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Carbamazepine
Selected AbstractsFactors affecting the degradation of pharmaceuticals in agricultural soils,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2009Sara C. Monteiro Abstract Pharmaceuticals may be released to the soil environment through the application of biosolids to land. To understand those factors affecting the persistence of pharmaceuticals in the soil environment, the present study was performed to assess the effects of soil type, the presence of biosolids, and the impact of chemical mixture interactions on the degradation of three pharmaceuticals: naproxen, carbamazepine, and fluoxetine. Single-compound studies showed that naproxen degraded in a range of soils with half-lives ranging from 3.1 to 6.9 d and in biosolids with a half-life of 10.2 d. No relationships were observed between degradation rate and soil physicochemical properties and soil bioactivity. For naproxen, addition of biosolids to soils reduced the degradation rate observed in the soil-only studies, with half-lives in the soil-biosolid systems ranging from 3.9 to 15.1 d. Carbamazepine and fluoxetine were found to be persistent in soils, biosolids, and soil-biosolid mixtures. When degradation was assessed using a mixture of the three study compounds and the sulfonamide antibiotic sulfamethazine, the degradation behavior of fluoxetine and carbamazepine was similar to that observed in the single compound studies (i.e., no degradation). However, the degradation rate of naproxen in soils, biosolids, and soil-biosolid systems spiked with the mixture was significantly slower than in the single-compound studies. As degradation studies for risk assessment purposes are performed using single substances in soil-only studies, it is possible that current risk assessment procedures will underestimate environmental impacts. Further work is therefore warranted on a larger range of substances, soils, biosolid types, and chemical mixtures to better understand the fate of pharmaceuticals in terrestrial systems. [source] A Comparative Pharmacokinetic Study in Healthy Volunteers of the Effect of Carbamazepine and Oxcarbazepine on Cyp3a4EPILEPSIA, Issue 3 2007Astrid-Helene Andreasen Summary:,Purpose: Carbamazepine (CBZ) and oxcarbazepine (OXCZ) are well-known inducers of drug metabolism via CYP3A4. Indirect interaction studies and clinical experience suggest that CBZ has a stronger potential in this regard than OXCZ. However this has never been subject to a direct comparative study. We performed a study in healthy volunteers to investigate the relative inductive effect of CBZ and OXCZ on CYP3A4 activity using the metabolism of quinidine as a biomarker reaction. Methods: Ten healthy, male volunteers participated in an open, randomized crossover study consisting of two periods separated by a 4-week wash-out period. The subjects received 1200 mg oral OXCZ daily for 17 days and 800 mg oral CBZ for 17 days. A single 200 mg oral dose of quinidine was administered at baseline and following administration of CBZ and OXCZ. Outcome parameters were the formation clearance of 3-hydroxyquinidine dose and the ratio of the AUCs of 3-hydroxyquinidine to quinidine. Results: Formation clearance of 3-hydroxyquinidine was increased by means of 89% (CI: 36,164; p = 0.0022) and 181% (CI: 120,260, p < 0.0001) after treatment with OXCZ and CBZ, respectively, compared to baseline. The relative inductive effect of CBZ was 46% higher than for OXCZ. AUC ratio increased by means of 161% (CI: 139,187, p < 0.0001) (OXCZ) and 222% (CI: 192,257, p < 0.0001) (CBZ). Quinidine Cmax decreased by means of 29% (CI: 16,40, p = 0.0018) (OXCZ) and 33% (CI: 18,45, p = 0.0020) (CBZ). T½ decreased by means of 12% (CI: 6,17, p < 0.0014) (OXCZ) and 32% (CI: 25,38, p < 0.0001) (CBZ). tmax was not changed in either period. Conclusion: We confirm a clinically significant inductive effect of both OXCZ and CBZ. The inductive effect of CBZ was about 46% higher than that of OXCZ, a difference that may be of clinical relevance. [source] Vitamin D Levels and Bone Turnover in Epilepsy Patients Taking Carbamazepine or OxcarbazepineEPILEPSIA, Issue 3 2006Scott Mintzer Summary:,Purpose: Evidence suggests that enzyme-inducing antiepileptic drugs (AEDs) may decrease serum 25-hydroxyvitamin D (25-OHD) levels and increase bone turnover. We sought to determine whether these are affected by treatment with carbamazepine (CBZ) or oxcarbazepine (OXC). Methods: We measured serum levels of 25-OHD, parathyroid hormone (PTH), osteocalcin (OCLN), bone alkaline phosphatase (BAP), and urinary N-telopeptides of type I collagen cross-links (NTX) in normal controls (n = 24) and in epilepsy patients taking CBZ (n = 21) or OXC (n = 24) in monotherapy. CBZ patients were subsequently switched overnight to OXC monotherapy, and after 6 weeks, the tests were repeated. Results: 25-OHD levels were lower in each drug-treated group (OXC, 19.4 ± 2.3 pg/ml; CBZ, 20.4 ± 2.4) than in the controls (27.5 ± 2.8) (ANOVA, p = 0.052). This difference was significant for the OXC group (p < 0.05). PTH, BAP, and NTX did not differ significantly among groups. OCLN levels were somewhat elevated in the OXC group (2.79 ± 0.47 ng/ml) and more clearly and significantly elevated in the CBZ group (3.63 ± 0.36) compared with controls (2.38 ± 0.41) (p = 0.053). Because the data were very similar between OXC and CBZ groups, they were combined to increase statistical power. The combined drug-treatment group had significantly higher BAP (p = 0.02) and lower 25-OHD (p = 0.015) than did controls. The latter remained significant even after accounting for the confounding effects of age on 25-OHD levels (p < 0.05). No significant differences were found after CBZ patients were switched to OXC. Conclusions: Epilepsy patients taking OXC or CBZ have significantly lower 25-OHD than do normal controls, with a pattern of changes in other bone biomarkers suggestive of secondary hyperparathyroidism. It may be prudent for patients taking CBZ or OXC to be prescribed 25-OHD replacement. [source] Pregabalin Drug Interaction Studies: Lack of Effect on the Pharmacokinetics of Carbamazepine, Phenytoin, Lamotrigine, and Valproate in Patients with Partial EpilepsyEPILEPSIA, Issue 9 2005Martin J. Brodie Summary:,Purpose: Pregabalin (PGB) is an ,2 -, ligand with demonstrated efficacy in epilepsy, neuropathic pain, and anxiety disorders. PGB is highly efficacious as adjunctive therapy in patients with refractory partial seizures. Methods: Given its efficacy as adjunctive therapy, the potential for interaction of PGB with other antiepileptic drugs (AEDs) was assessed in patients with partial epilepsy in open-label, multiple-dose studies. Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ). Results: Trough steady-state concentrations of CBZ (and its epoxide metabolite), PHT, LTG, and VPA were unaffected by concomitant PGB administration. Likewise, PGB steady-state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone. The PGB,AED combinations were generally well tolerated. PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug,drug interactions. [source] Time Course of Adverse Events in Patients with Localization-related Epilepsy Receiving Topiramate Added to CarbamazepineEPILEPSIA, Issue 5 2005Jerzy Majkowski Summary:,Purpose: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. Methods: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (,5% incidence) AEs were calculated for patients completing the 12-week study. Results: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. Conclusions: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy. [source] Carbamazepine Enhances Discriminative Memory in a Rat Model of EpilepsyEPILEPSIA, Issue 11 2004Rosane B. Bernardi Summary:,Purpose:,Seizures and antiepileptic drugs (AEDs) are the main causes for cognitive impairment in persons with epilepsy. It is still a matter of debate whether carbamazepine (CBZ) improves cognition because of its own psychotropic effects or because it is more effective to treat temporal epilepsy. Our objective was to analyze the performance of CBZ-treated or nontreated pilocarpine epileptic rats in an object-recognition test. Methods:,Twelve chronic pilocarpine-induced epileptic rats were treated with CBZ, 40 mg/kg, or saline, t.i.d. for 8 days. Twenty-one nonepileptic controls were treated with CBZ or saline. On day 8 of treatment, all rats were tested with an object-recognition paradigm. Results:,No locomotor impairment was detected in chronic epilepsy or CBZ treatment, as exploration during training was not affected. Exploratory behaviors during the choice session were not decreased in rats treated with CBZ; therefore CBZ does not compromise procedural memory. Epileptic rats showed a nonsignificant change in the discrimination performance, and prolonged treatment with CBZ in epileptic rats induced a significant increase in object discrimination during the choice session. Conclusions:,Even though pilocarpine-induced epileptic animals do not show compromised performance in the spontaneous object-recognition test, prolonged CBZ treatment has a positive effect on a simple object-discrimination task. These results may be associated with the psychotropic effects of CBZ. [source] Thyroid Function in Girls with Epilepsy with Carbamazepine, Oxcarbazepine, or Valproate Monotherapy and after Withdrawal of MedicationEPILEPSIA, Issue 3 2004Leena K. Vainionpää Summary: Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment. Methods: Forty-one girls taking VPA, 19 taking CBZ, and 18 taking OXC for epilepsy, as well as 54 healthy age-matched controls, aged 8 to 18 years, participated in the study. All the girls were examined clinically, and their pubertal stage was assessed. Blood samples were obtained for thyroid hormone and antibody assays. These examinations were repeated after a mean follow-up of 5.8 years to assess thyroid function, and 64 (82%) of 78 patients and 42 (78%) of 54 controls agreed to participate in the second evaluation. Results: In the first evaluation, the mean serum thyroid hormone concentrations were lower in the girls taking CBZ [thyroxine (T4), 70.2; SD, 10.9 nM; and free thyroxine (FT4), 11.5; SD, 1.8 pM] or OXC (T4, 74.9; SD, 16.4 nM; and FT4, 11.3; SD, 1.8 pM) than in the control girls (T4, 96.6; SD, 15.1 nM, and FT4, 14.4; SD, 1.5 pM; p < 0.001, all comparisons). However, thyrotropin (TSH) concentrations were normal in the girls taking CBZ or OXC. Sixty-three% of the girls taking CBZ and 67% of the girls taking OXC had serum T4 and/or FT4 levels below the lower limit of the reference range. The VPA-treated girls with epilepsy had normal serum T4 and FT4 concentrations, but slightly increased TSH levels (3.3; SD, 1.5 mU/L; p < 0.01) compared with the control girls (2.5; SD, 1.0 mU/L). Normal serum hormone concentrations were restored in the patients who discontinued the medication. Conclusions: Both CBZ and OXC reduce serum thyroid hormone concentrations in girls with epilepsy. Conversely, VPA is associated with normal serum thyroid hormone and increased thyrotropin levels. However, our results suggest that the changes in serum thyroid hormone and thyrotropin levels are reversible after withdrawal of the medication. [source] Comparative Cognitive Effects of Carbamazepine and Gabapentin in Healthy Senior AdultsEPILEPSIA, Issue 6 2001Roy Martin Summary: ,Purpose: This study compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in healthy senior adults by using a randomized, double-blind crossover design. Methods: Thirty-four senior adults were randomized to receive one of the two drugs followed by a 5-week treatment period. A 4-week washout phase preceded initiation of the second drug. Antiepileptic drugs (AEDs) were titrated to target doses of either CBZ (800 mg/day) or GBP (2,400 mg/day). Primary outcome measures were standardized neuropsychological tests of attention/vigilance, psychomotor speed, motor speed, verbal and visual memory, and the Profile of Mood State (POMS), yielding a total of 17 variables. Each subject received cognitive testing at predrug baseline, end of first drug phase, end of second drug phase, and 4 weeks after completion of the second drug phase. Results: Fifteen senior adults (mean age, 66.5 years; range, 59,76 years) completed the study. Seniors completing the study did not differ significantly from noncompleting seniors in terms of demographic features or baseline cognitive performances. Fifteen of the 19 seniors not completing the study dropped out while receiving CBZ. Adverse events were frequently reported for both AEDs, although they were more common for CBZ. Mean serum levels for the completers were within midrange clinical doses (CBZ, 6.8 ,g/ml; GBP, 7.1 ,g/ml). Significant differences between CBZ and GBP were found for only one of 11 cognitive variables, with better attention/vigilance for GBP, although the effect was modest. Performances on the nondrug average were significantly better on 45% of cognitive variables compared with CBZ and 36% compared with GBP. The overall pattern of means favored GBP over CBZ on 15 of 17 (p < 0.001), nondrug over CBZ on 17 of 17 (p < 0.0000), and nondrug over GBP on eight of 17 (NS). Conclusions: Mild cognitive effects were found for both AEDs compared with the nondrug average condition. The magnitude of difference between the two AEDs across the cognitive variables was modest. Self-reported mood was not significantly affected by either AED. However, overall tolerability and side-effect profile of CBZ were poorer than those of GBP in senior adults at doses and titration rates reported in this study. [source] Antiepileptogenesis and Seizure Prevention Trials with Antiepileptic Drugs: Meta-Analysis of Controlled TrialsEPILEPSIA, Issue 4 2001Nancy R. Temkin Summary: ,Purpose: To synthesize evidence concerning the effect of antiepileptic drugs (AEDs) for seizure prevention and to contrast their effectiveness for provoked versus unprovoked seizures. Methods: Medline, Embase, and The Cochrane Clinical Trials Register were the primary sources of trials, but all trials found were included. Minimal requirements: seizure-prevention outcome given as fraction of cases; AED or control assigned by random or quasi-random mechanism. Single abstracter. Aggregate relative risk and heterogeneity evaluated using Mantel,Haenszel analyses; random effects model used if heterogeneity was significant. Results: Forty-seven trials evaluated seven drugs or combinations for preventing seizures associated with fever, alcohol, malaria, perinatal asphyxia, contrast media, tumors, craniotomy, and traumatic brain injury. Effective: Phenobarbital for recurrence of febrile seizures [relative risk (RR), 0.51; 95% confidence interval (CI), 0.32,0.82) and cerebral malaria (RR, 0.36; CI, 0.23,0.56). Diazepam for contrast media,associated seizures (RR, 0.10; CI, 0.01,0.79). Phenytoin for provoked seizures after craniotomy or traumatic brain injury (craniotomy: RR, 0.42; CI, 0.25,0.71; TBI: RR, 0.33; CI, 0.19,0.59). Carbamazepine for provoked seizures after traumatic brain injury (RR, 0.39; CI, 0.17,0.92). Lorazepam for alcohol-related seizures (RR, 0.12; CI, 0.04,0.40). More than 25% reduction ruled out valproate for unprovoked seizures after traumatic brain injury (RR, 1.28; CI, 0.76,2.16), and carbamazepine for unprovoked seizures after craniotomy (RR, 1.30; CI, 0.75,2.25). Conclusions: Effective or promising results predominate for provoked (acute, symptomatic) seizures. For unprovoked (epileptic) seizures, no drug has been shown to be effective, and some have had a clinically important effect ruled out. [source] A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add-On Therapy to Carbamazepine in Patients with Partial-Onset SeizuresEPILEPSIA, Issue 9 2000A. P. Aldenkamp Summary: Purpose: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerabil-ity and prevents cognitive impairment. Methods: The study is a multicenter, randomized, observer-blinded, parallel-group clinical trial with VPA or TPM given as first-line add-on therapy to steady-state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25-mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach. Results: For the 10 baseline-to-end point comparisons, one test measuring short-term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline-to-titration comparisons also show one statistically significant difference, again for a test measuring short-term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration. Conclusion: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD). [source] The Anticonvulsant SGB-017 (ADCI) Blocks Voltage-Gated Sodium Channels in Rat and Human Neurons: Comparison with CarbamazepineEPILEPSIA, Issue 3 2000Lucy Sun Summary: Purpose: SGB-017 (ADCI) is a novel anticonvul-sant that blocks both voltage-activated sodium channels and N -methyl- d -aspartate (NMDA)-receptor-gated channels. Results by Rogawski et al. suggested that SGB-017 produces its anticonvulsant action primarily by inhibition of NMDA-receptor channels. However, SGB-017 is effective in several animal models of epilepsy that are unresponsive to NMDA antagonists. These results indicate that block of NMDA-receptor channels is not the only mechanism contributing to its anticonvulsant activity. Thus the effects of SGB-017 on neu-ronal sodium channels were investigated. Methods: Whole cell voltage-clamp techniques were used to record sodium currents in freshly dissociated rat superior cervical ganglion (SCG) and hippocampal neurons and cultured human NT2 neurons. The effects of SGB-017 on the amplitude of sodium currents, elicited by a depolarizing pulse to 0 mV from different holding potentials, were measured and compared with those of carbamazepine (CBZ). Results: SGB-017 inhibited sodium currents in rat SCG and hippocampal neurons with a similar potency to CBZ. Like CBZ, the inhibition of sodium channels by SGB-017 was voltage dependent. Its median inhibitory concentration (IC50) for inhibition of sodium channels at depolarized holding potentials is similar to that for its inhibition of NMDA receptor channels. In human hNT2 neurons, SGB-017 was more potent than CBZ at inhibiting sodium currents. Conclusions: SGB-017 produces its anticonvulsant activity by blocking both sodium- and NMDA-receptor channels in a voltage- and use-dependent manner. The combination of these two mechanisms of action makes SGB-017 an effective AED in several different animal models of epilepsy. [source] AAN-EFNS guidelines on trigeminal neuralgia managementEUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2008G. Cruccu Several issues regarding diagnosis, pharmacological treatment, and surgical treatment of trigeminal neuralgia (TN) are still unsettled. The American Academy of Neurology and the European Federation of Neurological Societies launched a joint Task Force to prepare general guidelines for the management of this condition. After systematic review of the literature the Task Force came to a series of evidence-based recommendations. In patients with TN MRI may be considered to identify patients with structural causes. The presence of trigeminal sensory deficits, bilateral involvement, and abnormal trigeminal reflexes should be considered useful to disclose symptomatic TN, whereas younger age of onset, involvement of the first division, unresponsiveness to treatment and abnormal trigeminal evoked potentials are not useful in distinguishing symptomatic from classic TN. Carbamazepine (stronger evidence) or oxcarbazepine (better tolerability) should be offered as first-line treatment for pain control. For patients with TN refractory to medical therapy early surgical therapy may be considered. Gasserian ganglion percutaneous techniques, gamma knife and microvascular decompression may be considered. Microvascular decompression may be considered over other surgical techniques to provide the longest duration of pain freedom. The role of surgery versus pharmacotherapy in the management of TN in patients with multiple sclerosis remains uncertain. [source] Using terahertz pulsed spectroscopy to quantify pharmaceutical polymorphism and crystallinityJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2005Clare J. Strachan Abstract Terahertz pulsed spectroscopy (TPS) is a new technique that is capable of eliciting rich information when investigating pharmaceutical materials. In solids, it probes long-range crystalline lattice vibrations and low energy torsion and hydrogen bonding vibrations. These properties make TPS potentially an ideal tool to investigate crystallinity and polymorphism. In this study four drugs with different solid-state properties were analyzed using TPS and levels of polymorphism and crystallinity were quantified. Carbamazepine and enalapril maleate polymorphs, amorphous, and crystalline indomethacin, and thermotropic liquid crystalline and crystalline fenoprofen calcium mixtures were quantified using partial least-squares analysis. Root-mean-squared errors of cross validation as low as 0.349% and limits of detection as low as approximately 1% were obtained, demonstrating that TPS is an analytical technique of potential in quantifying solid-state properties of pharmaceutical compounds. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:837,846, 2005 [source] Continuous venovenous hemodiafiltration to treat controlled-release carbamazepine overdose in a pediatric patientPEDIATRIC ANESTHESIA, Issue 11 2006TULAY SAHIN YILDIZ MD Summary Carbamazepine (CBZ) intoxication is an important issue in acute poisoning practice. Highly protein-bound, CBZ is not removed efficiently through conventional hemodialysis. We describe the use of continuous venovenous hemodiafiltration (CVVHDF) in a 2-year-old boy who developed general tonic clonic seizure and respiratory depression due to controlled-release formula of CBZ overdose (peak drug level of >20 ,g·ml,1, therapeutic range: 5,10 ,g·ml,1). Serum CBZ concentrations fell to 0.25 ,g·ml,1 at the end of hemodiafiltration. The patient recovered rapidly and was discharged from hospital 4 days from the time of ingestion with no complications or neurologic impairment. [source] Update on Anticonvulsants for the Treatment of Alcohol WithdrawalTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 2001Robert Malcolm M.D. Some anticonvulsants have been shown to be as effective as some benzodiazepines for the treatment of alcohol withdrawal. Anticonvulsants may offer advantages over benzodiazepines in the outpatient treatment of alcohol withdrawal: they lack abuse potential, have minimal interactions with alcohol, and may be more effective in ameliorating psychiatric symptoms of alcohol withdrawal. Carbamazepine appears to be as effective as lorazepam and oxazepam in ameliorating the symptoms of alcohol withdrawal. In addition, a recent study indicates that carbamazepine may suppress post-withdrawal alcohol use. Divalproex may also reduce symptoms of alcohol withdrawal, based on several open-label studies. However, both carbamazepine and divalproex have limited usefulness in alcoholics with severe hepatic or hematologic complications. Newer anticonvulsants, such as gabapentin and vigabatrin, also appear to reduce alcohol withdrawal symptoms in preclinical and open-label clinical trials while lacking the toxicities of carbamazepine and divalproex. Controlled trials are underway exploring the efficacy and safety of newer anticonvulsants for the treatment of alcohol withdrawal. [source] Opinion of Belgian neurologists on antiepileptic drug treatment in 2006: Belgian study on epilepsy treatment (BESET-2)ACTA NEUROLOGICA SCANDINAVICA, Issue 6 2009B. Legros Objectives,,, (i) To describe the medical treatment of epilepsy in Belgium in 2006, (ii) to detect the presence or absence of consensus in epilepsy treatment and (iii) to analyze the evolution of the neurologists' opinion between 2003 and 2006. Materials and methods,,, In December 2006, 100 neurologists were interviewed with a structured questionnaire, based on ordinal four-point scales. The questionnaire contained questions on treatment choices in adult patients with epilepsy. The results of this survey were compared with results of a previous one done in 2003. Results,,, Initial monotherapy was the preferred treatment strategy. Valproate was first choice in idiopathic generalized epilepsy. Carbamazepine and oxcarbazepine were first choice in focal epilepsy with partial seizures. Valproate was also first choice in focal epilepsy with secondarily generalized seizures. New antiepileptic drugs were recommended in second line. However, in special treatment situations, they were considered first-line, e.g. lamotrigine in case of women in childbearing age. In comparison with 2003, there was a trend of using earlier the new antiepileptic drugs. Conclusions,,, In end 2006, carbamazepine, valproate and oxcarbazepine were considered to be first choice drugs, whereas other newer drugs, like lamotrigine, levetiracetam and topiramate were predominantly prescribed in second line. [source] Weight gain in bipolar disorder: pharmacological treatment as a contributing factorACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2008C. Torrent Objective:, The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder. Method:, Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder. Results:, Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight. Conclusion:, Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues. [source] Rapid-cycling bipolar disorder: effects of long-term treatmentsACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2003L. Tondo Objective: To compare responses to long-term treatment of rapid-cycling (RC) vs. non-RC bipolar disorder patients and assess relative effectiveness of specific agents in RC patients. Method: Studies identified by literature searching were analyzed for effects of RC status and treatment-type on clinical outcome (recurrence or non-improvement per exposure-time), using random-effects methods to estimate pooled rates and their 95% CI for quantitative meta-analytic modeling. Results: Data were obtained from 16 reports with 25 trial-arms involving 1856 (905 RC and 951 non-RC) patients treated with carbamazepine, lamotrigine, lithium, topiramate, or valproate, alone or with other agents over an average of 47.5 months (7347 total patient-years). Estimated RC prevalence was 15.4%. Crude rates (%/month) of recurrence (2.31/1.20) and clinical non-improvement (1.93/0.49) averaged 2.9-fold greater in RC vs. non-RC subjects. The pooled RC/non-RC risk ratio (RR) for inferior treatment-response (in 13 direct comparisons) was 1.40 (CI 1.26,1.56; P < 0.0001). Pooled crude recurrence and non-improvement rates suggested no clear advantage for any treatment, nor superiority for anticonvulsants over lithium. However, only lithium vs. carbamazepine could be directly compared (in four treatment-arms) meta-analytically in RC patients (RR = 0.93, CI 0.74,1.18, indicating no difference in effectiveness). Conclusion: As expected, RC was associated with lower effectiveness of all treatments evaluated. Direct comparisons of specific treatment alternatives for RC patients were rare, and provided no secure evidence of superiority of any treatment. Additional long-term studies comparing RC/non-RC patients randomized to specific treatments are required. [source] Post-dexamethasone cortisol correlates with severity of depression before and during carbamazepine treatment in women but not menACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2001Elizabeth A. Osuch Objective: ,Previous studies show a state-dependent relationship between depression and post-dexamethasone suppression test (DST) cortisol level, as well as differences in DST response with age and gender. Method: ,In this study, 74 research in-patients with affective disorders were given the DST on placebo and in a subgroup following treatment with carbamazepine. Depression was evaluated twice daily with the Bunney,Hamburg (BH) rating scale. Data were examined for the total subject population, by gender and by menopausal status in women. Results: ,A robust positive correlation was observed between depression severity and post-DST cortisol in pre- and postmenopausal females, but not in males. This relationship persisted in women when restudied on a stable dose of carbamazepine (n=42). Conclusion: ,The pathophysiological implications of this selective positive relationship between severity of depression and post-DST cortisol in women, but not men, should be explored further. [source] Preclinical abuse potential assessment of the anticonvulsant zonisamideDRUG DEVELOPMENT RESEARCH, Issue 2 2001Jenny L. Wiley Abstract Zonisamide (Zonegran®) is a broad-spectrum antiepileptic agent that shares some pharmacological properties with other anticonvulsants, including phenytoin, carbamazepine, and valproic acid, but is differentiated from these agents by the ability to significantly block T-type calcium channels. Zonisamide interacts with the ,-amino-butyric acid (GABA) receptor in an allosteric manner, and thus does not modulate GABA receptor effects. However, given the potential of drugs within the latter class for drug abuse in humans, an evaluation of zonisamide for abuse potential is an important component of its potential side-effect profile. In the present study, zonisamide was tested in animal models of the subjective and reinforcing effects of central nervous system (CNS) depressant drugs, e.g., diazepam discrimination in rats and intravenous self-administration in rhesus monkeys, respectively. In addition, zonisamide was evaluated for physical dependence liability in a chronic infusion model using rats. Zonisamide did not substitute for diazepam in rats trained to discriminate 2.5-mg/kg diazepam from vehicle nor was it self-administered by rhesus monkeys experienced in methohexital-reinforced responding. Continuous infusion of zonisamide (400 or 600 mg/kg/day) did not prevent the loss of body weight associated with discontinued pentobarbital infusion. These doses of zonisamide did produce some incomplete attenuation of observable signs of pentobarbital withdrawal, likely due to direct sedative or depressant effects of these high doses. These results suggest that zonisamide would not produce diazepam-like intoxication in humans nor would it likely be subject to abuse when made more widely available. Further, when administered chronically, zonisamide would not be expected to produce physical dependence of the CNS depressant type. Taken together, these results support the prediction that zonisamide would have low abuse liability. Drug Dev. Res. 54:66,74, 2001. © 2001 Wiley-Liss, Inc. [source] Cover Picture: Electrophoresis 22'2008ELECTROPHORESIS, Issue 22 2008Article first published online: 26 NOV 200 Regular issues provide a wide range of research and review articles covering all aspects of electrophoresis. Here you will find cutting-edge articles on methods and theory, instrumentation, nucleic acids, CE and CEC, miniaturization and microfluidics, proteomics and two-dimensional electrophoresis. Selected topics of issue 22 are: Microfluidics: Applications for analytical purposes in chemistry and biochemistry ((http://doi.wiley.com/10.1002/elps.200800121)) Simultaneous laser-induced fluorescence and retro-reflected beam interference detection for CE ((http://doi.wiley.com/10.1002/elps.200800292)) Quantitative Proteomics by Fluorescent Labeling of Cysteine Residues using a Set of Two Cyanine-based or Three Rhodamine-based Dyes ((http://doi.wiley.com/10.1002/elps.200800092)) Chemometric resolution of fully overlapped capillary electrophoresis peaks: quantitation of carbamazepine in human serum in the presence of several interferences ((http://doi.wiley.com/10.1002/elps.200800400)) Identification of inorganic ions in post-blast explosive residues using portable capillary electrophoresis instrumentation and capacitively-coupled contactless conductivity detection ((http://doi.wiley.com/10.1002/elps.200800226)) [source] Occurrence of pharmaceuticals and hormones in sewage sludgeENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2010Antonio Nieto Abstract The present study evaluates the presence of nine hormones and their conjugates and 20 pharmaceuticals such as anti-inflammatories, lipid regulators, and antibiotics among others in sewage sludge from two sewage treatment plants (STPs) in the Tarragona area (Spain) for the period March 2007 until March 2008. Target analytes have been determined using different methods involving pressurized liquid extraction and liquid chromatography (electrospray ionization) tandem mass spectrometry (MS-MS). Most of the pharmaceuticals and hormones were found at low micrograms per kilogram dry weight levels in the sewage sludge samples analyzed. Some compounds were present in all samples, such as acetaminophen, caffeine, carbamazepine, and ibuprofen, among others. Other compounds, such as estriol, were found only in the STP of Reus. The compounds that showed the highest concentration in both STPs were roxithromycin and tylosin (1,446 and 1,958,µg/kg dry wt, respectively). The presence of these compounds in sewage sludge demonstrated that they are partially or totally removed from the influent wastewater by sorption into the sewage sludge. Environ. Toxicol. Chem. 2010;29:1484,1489. © 2010 SETAC [source] Factors affecting the degradation of pharmaceuticals in agricultural soils,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2009Sara C. Monteiro Abstract Pharmaceuticals may be released to the soil environment through the application of biosolids to land. To understand those factors affecting the persistence of pharmaceuticals in the soil environment, the present study was performed to assess the effects of soil type, the presence of biosolids, and the impact of chemical mixture interactions on the degradation of three pharmaceuticals: naproxen, carbamazepine, and fluoxetine. Single-compound studies showed that naproxen degraded in a range of soils with half-lives ranging from 3.1 to 6.9 d and in biosolids with a half-life of 10.2 d. No relationships were observed between degradation rate and soil physicochemical properties and soil bioactivity. For naproxen, addition of biosolids to soils reduced the degradation rate observed in the soil-only studies, with half-lives in the soil-biosolid systems ranging from 3.9 to 15.1 d. Carbamazepine and fluoxetine were found to be persistent in soils, biosolids, and soil-biosolid mixtures. When degradation was assessed using a mixture of the three study compounds and the sulfonamide antibiotic sulfamethazine, the degradation behavior of fluoxetine and carbamazepine was similar to that observed in the single compound studies (i.e., no degradation). However, the degradation rate of naproxen in soils, biosolids, and soil-biosolid systems spiked with the mixture was significantly slower than in the single-compound studies. As degradation studies for risk assessment purposes are performed using single substances in soil-only studies, it is possible that current risk assessment procedures will underestimate environmental impacts. Further work is therefore warranted on a larger range of substances, soils, biosolid types, and chemical mixtures to better understand the fate of pharmaceuticals in terrestrial systems. [source] Evaluation of poly(ethylene-co-vinyl acetate-co-carbon monoxide) and polydimethylsiloxane for equilibrium sampling of polar organic contaminants in waterENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2009Jörgen A Magnér Abstract Abstract-The aim of the present study was to develop a passive a bsorptive equilibrium sampler that would enable the determination of the concentrations of polar organic compound (POC) in water more efficiently than existing techniques. To this end, a novel plastic material, poly(ethylene-co-vinyl acetate-co-carbon monoxide) (PEVAC), was evaluated and the results were compared with an existing silicone-based passive absorptive equilibrium device. Seven compounds (imidacloprid, carbendazim, metoprolol, atrazin, carbamazepine, diazinon, and chlorpyrifos), a mixture of pharmaceuticals, and pesticides with a logarithmic octanol-water partition coefficient ranging from 0.2 to 4.77 were selected as model substances for the experiments. The results showed that six of the seven selected POCs reached distribution equilibrium within 4 d in the two materials tested. A linear relation with a regression coefficient of more than 0.8906 between the established logarithmic absorbent-water partition coefficient and the calculated logarithmic dissociation partition coefficient of the selected compounds in the two polymers was observed. The correlation between these two coefficients was within one order of magnitude for the compounds that reached equilibrium in the two polymers, which demonstrates that both materials are suitable for mimicking biological uptake of POCs. The PEVAC material showed an enhanced sorption for all selected compounds compared to the silicone material and up to five times higher enrichment for the most polar compound. Fluorescence analysis of the sampler cross-section, following the uptake of fluoranthene, and proof that the sorption was independent of surface area variations demonstrated that the PEVAC polymer possessed absorptive rather than adsorptive enrichment of organic compounds. [source] Wastewater treatment plants as a pathway for aquatic contamination by pharmaceuticals in the Ebro river basin (Northeast Spain)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007Meritxell Gros Abstract The occurrence of 28 pharmaceuticals of major human consumption in Spain, including analgesics and anti-inflam-matories, lipid regulators, psychiatric drugs, antibiotics, antihistamines, and ,-blockers, was assessed along the Ebro river basin, one of the biggest irrigated lands in that country. Target compounds were simultaneously analyzed by off-line solid-phase extraction, followed by liquid chromatography-tandem mass spectrometry. The loads of detected pharmaceuticals and their removal rates were studied in seven wastewater treatment plants (WWTPs) located in the main cities along the basin. Total loads ranged from 2 to 5 and from 0.5 to 1.5 g/d/1,000 inhabitants in influent and effluent wastewaters, respectively. High removal rates (60,90%) were achieved mainly for analgesics and anti-inflammatories. The other groups showed lower rates, ranging from 20 to 60%, and in most cases, the antiepileptic carbamazepine, macrolide antibiotics, and trimethoprim were not eliminated at all. Finally, the contribution of WWTP effluents to the presence of pharmaceuticals in receiving river waters was surveyed. In receiving surface water, the most ubiquitous compounds were the analgesics and anti-inflammatories ibuprofen, diclofenac, and naproxen; the lipid regulators bezafibrate and gemfibrozil; the antibiotics erythromycin, azithromycin, sulfamethoxazole, trimethoprim, and less frequently, ofloxacin; the antiepileptic carbamazepine; the antihistamine ranitidine; and the ,-blockers atenolol and sotalol. Although levels found in WWTP effluents ranged from low ,g/L to high ng/L, pharmaceuticals in river waters occurred at levels at least one order of magnitude lower (low ng/L range) because of dilution effect. From the results obtained, it was proved that WWTP are hot spots of aquatic contamination concerning pharmaceuticals of human consumption. [source] Seasonality effects on pharmaceuticals and s -triazine herbicides in wastewater effluent and surface water from the Canadian side of the upper Detroit RiverENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2006Wen Yi Hua Abstract The influence of seasonal changes in water conditions and parameters on several major pharmacologically active compounds (PhACs) and s -triazine herbicides was assessed in the wastewater and sewage treatment plant (WSTP) effluent as well as the downstream surface water from sites on the Canadian side of the upper Detroit River, between the Little River WSTP and near the water intake of a major drinking water treatment facility for the City of Windsor (ON, Canada). The assessed PhACs were of neutral (carbamazepine, cotinine, caffeine, cyclophosphamide, fluoxetine, norfluoxetine, pentoxifylline, and trimethoprim) and acidic (ibuprofen, bezafibrate, clofibric acid, diclofenac, fenoprofen, gemfibrozil, indomethacin, naproxen, and ketoprofen) varieties. The major assessed s -triazine herbicides were atrazine, simazine, propazine, prometon, ametryn, prometryn, and terbutryn. At sampling times from September 2002 to June 2003, 15 PhACs were detected in the WSTP effluent at concentrations ranging from 1.7 to 1,244 ng/L. The PhAC concentrations decreased by as much 92 to 100% at the Little River/Detroit River confluence because of the river dilution effect, with further continual decreases at sites downstream from the WSTP. The only quantifiable s -triazine in WSTP effluent, atrazine, ranged from 6.7 to 200 ng/L and was higher in Detroit River surface waters than in WSTP effluent. Only carbamazepine, cotinine, and atrazine were detectable at the low-nanogram and subnanogram levels in surface waters near a drinking water intake site. Unlike the PhACs, atrazine in the Detroit River is not attributable to point sources, and it is heavily influenced by seasonal agricultural usage and runoff. Detroit River surface water concentrations of carbamazepine, cotinine, and atrazine may present a health concern to aquatic wildlife and to humans via the consumption of drinking water. [source] Presence and distribution of wastewater-derived pharmaceuticals in soil irrigated with reclaimed waterENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2006Chad A. Kinney Abstract Three sites in the Front Range of Colorado, USA, were monitored from May through September 2003 to assess the presence and distribution of pharmaceuticals in soil irrigated with reclaimed water derived from urban wastewater. Soil cores were collected monthly, and 19 pharmaceuticals, all of which were detected during the present study, were measured in 5-cm increments of the 30-cm cores. Samples of reclaimed water were analyzed three times during the study to assess the input of pharmaceuticals. Samples collected before the onset of irrigation in 2003 contained numerous pharmaceuticals, likely resulting from the previous year's irrigation. Several of the selected pharmaceuticals increased in total soil concentration at one or more of the sites. The four most commonly detected pharmaceuticals were erythromycin, carbamazepine, fluoxetine, and diphenhydramine. Typical concentrations of the individual pharmaceuticals observed were low (0.02,15 ,g/kg dry soil). The existence of subsurface maximum concentrations and detectable concentrations at the lowest sampled soil depth might indicate interactions of soil components with pharmaceuticals during leaching through the vadose zone. Nevertheless, the present study demonstrates that reclaimed-water irrigation results in soil pharmaceutical concentrations that vary through the irrigation season and that some compounds persist for months after irrigation. [source] Hyperhomocysteinemia in epileptic patients on new antiepileptic drugsEPILEPSIA, Issue 2 2010Vincenzo Belcastro Summary Purpose:, Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. Methods:, Patients 18,50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B12, and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. Results:, Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 ,m; physiologic range 5,13 ,m] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) ,m, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) ,m]. Discussion:, Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy. [source] Ghrelin levels are reduced in prepubertal epileptic children under treatment with carbamazepine or valproic acidEPILEPSIA, Issue 2 2010Flavia Prodam Summary A relationship between ghrelin and epilepsy has been already shown in humans, although the results are controversial. Ghrelin levels are reduced in obesity. Epileptic patients progressively develop a therapy-linked weight gain; however, the mechanisms for this have not been fully explained. The aim of our study is to evaluate if ghrelin secretion is modulated by treatment with carbamazepine or valproic acid in young prepubertal epileptic children. Ghrelin levels were reduced in normal-weight young epileptic prepubertal children under treatment with carbamazepine (p < 0.0001) or valproic acid (p < 0.006) compared to healthy age- and weight-matched subjects. Ghrelin was also lower in children under carbamazepine when compared to those under valproic acid (p < 0.01). A derangement in ghrelin secretion in epilepsy during specific pharmacologic therapies and independent of weight gain could be hypothesized. [source] Cardiac function and antiepileptic drug treatment in the elderly: A comparison between lamotrigine and sustained-release carbamazepineEPILEPSIA, Issue 8 2009Erik Saetre Summary Purpose:, To investigate the comparative effects of carbamazepine (CBZ) and lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients with newly diagnosed epilepsy. Methods:,, The study was conducted in the Norwegian subcohort (n = 108) of an international randomized double-blind 40-week trial, which compared the efficacy and tolerability of LTG and sustained-release CBZ in patients aged 65 and older with newly diagnosed epilepsy. Target maintenance doses were 400 mg/day for CBZ and 100 mg/day for LTG, with adjustments based on clinical response. Patients with significant unpaced atrioventricular (AV) conduction defect were excluded. Resting 12-lead ECG recordings were made under standardized conditions at pretreatment (baseline) and at the 40-week study visit (treatment visit). Changes in QRS interval (primary endpoint), heart rate (HR), PQ, and QTc (HR-corrected QT) intervals were assessed and compared between groups. Results:, Of the 108 patients randomized, 33 discontinued prematurely because of adverse events (n = 24, none of which was cardiac) or other reasons (n = 9), and 15 were nonevaluable due to incomplete ECG data. None of the assessed ECG parameters differed significantly between groups at baseline. No significant ECG changes were recorded between baseline and treatment visit for QRS duration and QTc intervals, whereas HR fell and PQ intervals increased slightly on both treatments. However, there were no differences between groups in changes from baseline to treatment visit. There were no significant relationships between individual ECG changes and serum drug concentrations, except for QTc intervals, which decreased slightly with increasing CBZ concentrations. The proportion of patients with ECG parameters outside the normal range at treatment visit was similar to that recorded at baseline. Discussion:, Clinically significant ECG changes are not common during treatment with CBZ or LTG in elderly patients with no preexisting significant AV conduction defects. [source] | ||||||||||||||||||||||||||||||||||||||||