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Mg Tablets (mg + tablet)
Selected AbstractsScreening Tablets for DOB Using Surface-Enhanced Raman Spectroscopy,JOURNAL OF FORENSIC SCIENCES, Issue 5 2007Steven E. J. Bell Ph.D. Abstract:, 2,5,-Dimethoxy-4-bromoamphetamine (DOB) is of particular interest among the various "ecstasy" variants because there is an unusually long delay between consumption and effect, which dramatically increases the danger of accidental overdose in users. Screening for DOB in tablets is problematic because it is pharmacologically active at 0.2,3 mg, which is c. 50 times less than 3,4-methylenedioxy-N-methylamphetamine (MDMA) and makes it more difficult to detect in seized tablets using conventional spot tests. The normal Raman spectra of seized DOB tablets are dominated by the bands of the excipient with no evidence of the drug component. Here we report the first use of on-tablet surface-enhanced Raman spectroscopy (SERS) to enhance the signal from a low concentration drug. Raman studies (785-nm excitation) were carried on series of model DOB/lactose tablets (total mass c. 400 mg) containing between 1 mg and 15 ,g of DOB and on seized DOB tablets. To generate surface-enhanced spectra, 5 ,L of centrifuged silver colloid was dispensed onto the upper surface of the tablets, followed by 5 ,L of 1.0 mol/dm3 NaCl. The probe laser was directed onto the treated area and spectra accumulated for c. 20 sec (10 sec × 2). It was found that the enhancement of the DOB component in the model tablets containing 1 mg DOB/tablet and in the seized tablets tested was so large that their spectra were completely dominated by the vibrational bands of DOB with little or no contribution from the unenhanced lactose excipient. Indeed, the most intense DOB band was visible even in tablets containing just 15 ,g of the drug. On-tablet surface-enhanced Raman spectroscopy is a simple method to distinguish between low dose DOB tablets and those with no active constituent. The fact that unique spectra are obtained allows identification of the drug while the lack of sample preparation and short signal accumulation times mean that the entire test can be carried out in <1 min. [source] Amlodipine bioequivalence study: quantification by liquid chromatography coupled to tandem mass spectrometryBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2001M. Carvalho Abstract Objective,To assess the bioequivalence of two amlodipine tablet formulations (Amlodipine® 5 mg tablet from Merck S.A. Indústrias Químicas, Brazil as test formulation and Norvasc® 5 mg tablet from Laboratórios Pfizer Ltd., Brazil as reference formulation) in 24 healthy volunteers of both sexes. Methods,The study was conducted using an open, randomized two-period crossover design with a 4-week washout interval. Plasma samples were obtained over a 144 h period. Plasma amlodipine concentrations were analyzed by combined liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the amlodipine plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUClast, AUC0,inf and Cmax. The statistical interval proposed was 80,125% according to the US Food and Drug Administration Agency. Results,The limit of quantification was 0.1 ng/ml for plasma amlodipine analysis. The geometric mean and the 90% confidence interval (CI) test/reference ratios were 101.2 (92.9,110.2%) for AUClast, 99.6 (91.5,108.4%) for AUC0,inf and 98.5 (89.0,109.1%) for Cmax. Conclusion,Since the 90% CI for AUClast, AUC0,inf and Cmax ratios were within in the 80,125% interval proposed by the US FDA, it was concluded that Amlodipine® 5 mg tablet (test formulation) was bioequivalent to Norvasc® 5 mg tablet, in terms of both rate and extent of absorption. Copyright © 2001 John Wiley & Sons, Ltd. [source] Effect of smoking on single dose pharmacokinetics of phenobarbitalBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2001A. Mirfazaelian Abstract In order to determine interaction of smoking with single dose pharmacokinetics of phenobarbital, a 60 mg tablet of the drug was given to 12 healthy male subjects in two groups (6 smokers and 6 non-smokers) in a double blind study. An HPLC method using UV detection was developed to assess phenobarbital in plasma of the subjects. Pharmacokinetic parameters were calculated and compared in the two groups. Pharmacokinetic parameters of the two groups were not significantly different in the two groups (p<0.05). The results show no considerable effect of cigarette smoking on phenobarbital pharmacokinetics, which is in agreement with enzyme studies performed previously. Copyright © 2001 John Wiley & Sons, Ltd. [source] A randomised comparison of oral misoprostol and vaginal prostaglandin E2 tablets in labour induction at termBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 5 2004A. Shetty Objective To compare the efficacy of 100 ,g of oral misoprostol with 3 mg prostaglandin E2 vaginal tablets in term labour induction. Design A non-blinded, randomised, controlled trial. Setting A tertiary level, teaching Scottish Hospital. Population Two hundred women at term with indications for labour induction and modified Bishop's cervical score of less than 8. Methods The women were randomly allocated to receive either 100 ,g of misoprostol orally (which could be repeated 4 hourly to a maximum of five doses if indicated), or a 3 mg tablet of prostaglandin E2 vaginally (which could be repeated in 6 hours, according to routine departmental protocol). Main outcome measure The number delivering vaginally within 24 hours of the induction. Results Seventy-five women delivered vaginally in the misoprostol group and 73 in the PGE2 group. Of these, 50.7% in the misoprostol group and 54.8% in the PGE2 group delivered within 24 hours of the induction (RR 0.92, 95% CI 0.7 to 1.3). More women in the misoprostol group were given oxytocin, but this was not statistically significant (60%vs 47%, RR 1.3, 95% CI 0.98 to 1.7). Two women in the misoprostol group had uterine hyperstimulation. The neonatal outcomes were not significantly different in the two groups. There was a £1100 saving on direct drug costs in the misoprostol group. Conclusions Oral misoprostol (100 ,g) has similar efficacy to vaginal PGE2 tablets, and may be an option to consider for term labour induction. [source] Pharmacokinetics of tibolone in early and late postmenopausal womenBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2002C. J. Timmer Aims, Tibolone is a tissue-specific compound with favourable effects on bone, vagina, climacteric symptoms, mood and sexual well being in postmenopausal women, without stimulating the endometrium or breast. Since tibolone is used for the treatment of both young and elderly postmenopausal women, its pharmacokinetics were studied to investigate potential differences with age. In addition, the bioequivalence of the 1.25 and 2.5 mg tablets was evaluated. Methods, Single doses of 1.25 or 2.5 mg of tibolone were given in a double-blind, randomized, two-way cross-over study to women aged between 45 and 55 years or between 65 and 75 years of age. Results, Age did not have a significant effect on Cmax, tmax, and t½ of tibolone and its metabolites and on the body weight standardized oral clearance (CL/F kg,1) of the 3,- and 3,-hydroxy tibolones. In early postmenopausal women, significantly lower values were found for the AUC(0,16 h), and AUC(0,,) of 3,-hydroxy tibolone 24.6±6.6 vs 29.2±4.9 and 27.1±6.9 vs 32.3±6.5 ng ml,1 h for the 1.25 mg tablet, respectively, and 45.4±13.9 vs 55.7±14.1 and 49.6±14.6 vs 62.6±17.3 ng ml,1 h for the 2.5 mg tablet, respectively. When these values were adjusted for the significantly higher body weight of the early postmenopausal women, the differences disappeared. No significant differences between early and late postmenopausal women were found for the AUC(0,8 h), and AUC(0,,) of 3,-hydroxy tibolone. The rate of absorption of tibolone and the rates of absorption or formation of the 3,- and 3,-hydroxy tibolones were significantly higher after the 1.25 mg dose than after the 2.5 mg tablet, resulting in increases of 32%, 27% and 17% for the dose normalized- Cmax of tibolone and the 3,- and 3,-hydroxy tibolones, respectively. tmax for tibolone and its metabolites was 12,27% less after 1.25 mg compared to 2.5 mg, which was statistically significant. The two formulations were bioequivalent with respect to the dose-normalized AUC(0,,) and the AUC(0,tfix) values for the 3,-hydroxy tibolone (ratio point estimate [90%, confidence limits]: 1.08 [1.04, 1.14] and 1.08 [1.03, 1.13], respectively) and for the 3,-hydroxy tibolone (1.07 [1.01, 1.14] and 1.04 [0.96, 1.12], respectively). Both formulations were also bioequivalent with respect to CL/F kg,1 and t½. Conclusions, The pharmacokinetics of tibolone are similar in early (age 45,55 years) and late (65,75 years) postmenopausal women. The 2.5 and 1.25 mg tablets are bioequivalent with respect to the extent of absorption. The rate of absorption or formation of the metabolites of tibolone were not bioequivalent, but these differences are considered to have no clinical relevance in view of the chronic administration of tibolone. [source] Treatment satisfaction and efficacy of the rapid release formulation of sumatriptan 100 mg tablets utilising an early intervention paradigm in patients previously unsatisfied with sumatriptanINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2008L. C. Newman Summary Aims:, To evaluate treatment satisfaction, efficacy and functional ability of the rapid release formulation of sumatriptan 100 mg tablets (sumatriptan RT 100 mg) in an early intervention paradigm in patients who were dissatisfied with low-dose sumatriptan and not completely satisfied with their current migraine regimen. Methods:, Experienced migraineurs who reported a mild migraine pain phase, dissatisfaction with the previous sumatriptan treatment and some dissatisfaction with their current treatment regimen had no experience with sumatriptan at the 100 mg dose were enrolled in an open-label, single group study. Subjects were instructed to treat four migraine attacks within 30 min of the onset of mild pain. Treatment satisfaction was measured with the Patient Perception of Migraine Questionnaire Revised version (PPMQ-R) questionnaire. Results:, More than half of the subjects were either very satisfied or satisfied with the efficacy of early intervention sumatriptan RT 100 mg after each attack and at the follow-up study visit. The mean total PPMQ-R score was 75.2 out of 100. Between 63% and 73% of subjects were pain-free within 4 h of dosing. Between 79% and 90% of subjects reported an ability to function normally within 4 h of taking the study medication. Conclusion:, Subjects who were previously unsatisfied with lower doses of sumatriptan and less than very satisfied with their current treatment regimen were more likely to be satisfied or very satisfied with sumatriptan RT 100 mg in an early intervention paradigm. Results were consistent across four migraine attacks and at a follow-up visit. The treatment satisfaction results corresponded with positive results on efficacy measures and a functional status measure. [source] A randomised comparison of oral desmopressin lyophilisate (MELT) and tablet formulations in children and adolescents with primary nocturnal enuresisINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2007H. Lottmann Summary Aims:, Desmopressin is a useful treatment for primary nocturnal enuresis (PNE), a common childhood condition that can persist into adolescence. This open-label, randomised, cross-over study evaluated the preference of children and adolescents with PNE for sublingual desmopressin oral lyophilisate (MELT) vs. tablet treatment, and the efficacy, safety, compliance and ease of use associated with each formulation. In total, 221 patients aged 5,15 years who were already receiving desmopressin tablets were randomised 1 : 1 to receive desmopressin treatment in the order MELT/tablet (n = 110) or tablet/MELT (n = 111) for 3 weeks each. Each formulation was administered in bioequivalent doses (0.2/0.4 mg tablets , 120/240 ,g MELT). Following treatment, patients were questioned regarding treatment preference. Diary card data and 100 mm Visual Analogue Scale scores were also recorded. Results:, Overall, patients preferred the MELT formulation to the tablet (56% vs. 44%; p = 0.112). This preference was age dependent (p = 0.006); patients aged < 12 years had a statistically significant preference for desmopressin MELT (p = 0.0089). Efficacy was similar for both formulations (MELT: 1.88 ± 1.94 bedwetting episodes/week; tablet: 1.90 ± 1.85 episodes/week). Ease of use of both formulations was high. Compliance (, 80%) was 94.5% for MELT patients vs. 88.9% for the tablet (p = 0.059). No serious/severe adverse events were reported. Conclusions:, There was an overall preference for the MELT, and a statistically significant preference for desmopressin MELT in children aged 5,11 years. Desmopressin MELT had similar levels of efficacy and safety at lower dosing levels than the tablet, and therefore facilitates early initiation of PNE treatment in children aged 5,6 years. [source] Crushed Clopidogrel Administered via Nasogastric Tube Has Faster and Greater Absorption than Oral Whole TabletsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2009M. UROOJ ZAFAR M.B.B.S. Objectives: To compare the absorption of 300 mg clopidogrel administered crushed via nasogastric (NG) tube versus whole tablets taken orally in healthy volunteers. Background: Earlier antiplatelet therapy has proven benefits in treatment of myocardial infarction and in patients undergoing PCI. Aspirin can be delivered early in crushed form via NG tube after CABG surgery to prevent graft occlusion. If clopidogrel given crushed via NG tube provides faster absorption, it could allow earlier clopidogrel loading. Methods: Nine healthy human subjects (34.7 ± 11.1 years, 5 males) were given 300 mg clopidogrel in crushed form via NG tube with 30 mL water after 8 hours of fasting. Plasma levels of the primary circulating inactive clopidogrel metabolite SR26334 were measured after 20 minutes, 40 minutes, 1, 2, 4, 8, 12, and 24 hours of dosing. Following ,2 week washout, same subjects swallowed 300 mg clopidogrel (four 75 mg tablets) after an 8-hour fasting and SR26334 levels were measured at the same time points. Results: Plasma SR26334 concentrations peaked earlier after crushed delivery than after oral intake (44 vs. 70 minutes, P = 0.023) and the median peak was 80% higher (13,083 vs. 7,255 ng/mL, respectively, P = 0.021). At 40 minutes, area under the curve was almost twofold greater with NG administration than oral administration (geometric means ratio = 0.5299, 95% CI = 0.28,0.99, P = 0.048), but was similar over the 24-hour period with both administration methods (geometric means ratio = 1.05, 95% CI = 0.84,1.32, P = 0.646). Conclusions: A 300 mg loading dose of crushed clopidogrel administered via NG tube provides faster and greater bioavailability than an equal dose taken orally as whole tablets. The clinical benefits of this strategy need to be investigated. [source] Biowaiver monographs for immediate release solid oral dosage forms: AciclovirJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2008J. Arnal Abstract Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing (biowaiver) for the approval of immediate release (IR) solid oral dosage forms containing aciclovir are reviewed. Aciclovir therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) studies were also taken into consideration in order to ascertain whether a biowaiver can be recommended. According to the Biopharmaceutics Classification System (BCS) and considering tablet strengths up to 400 mg, aciclovir would be BCS Class III. However, in some countries also 800 mg tablets are available which fall just within BCS Class IV. Aciclovir seems not to be critical with respect to a risk for bioinequivalence, as no examples of bioinequivalence have been identified. It has a wide therapeutic index and is not used for critical indications. Hence, if: (a) the test product contains only excipients present in aciclovir solid oral IR drug products approved in ICH or associated countries, for instance as presented in this article; and (b) the comparator and the test product both are very rapidly dissolving, a biowaiver for IR aciclovir solid oral drug products is considered justified for all tablet strengths. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5061,5073, 2008 [source] Clinical trial: oral colon-release parnaparin sodium tablets (CB-01-05 MMX®) for active left-sided ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010G. CELASCO Aliment Pharmacol Ther 31, 375-386 Summary Background, The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX®) has been proposed as a novel approach for the treatment of ulcerative colitis (UC). Aim, To assess the efficacy and the tolerability of 8 weeks' oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates. Methods, This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX® 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS). Results, A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX® group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005). Conclusions, CB-01-05 MMX® was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates. [source] Pilot study: the use of sulfasalazine for the treatment of acute pouchitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010A. BELLUZZI Summary Background, Acute pouchitis, an idiopathic inflammatory condition of the ileal pouch anal anastomosis, is the most frequent complication after proctocolectomy for ulcerative colitis. Aim, To test the hypothesis that sulfasalazine (SASP) might have a synergistic beneficial effect in acute pouchitis, by combining the anti-inflammatory activity of 5-aminosalicylic Acid and the bacteriostatic effect of sulphapyridine. Methods, Twenty two patients were investigated for acute pouchitis; the Pouchitis Disease Activity Index (PDAI) was calculated and 11 patients with acute pouchitis (PDAI >7) were included in an open study, after obtaining their informed consent. Patients were treated with SASP 500 mg tablets, two tablets three times per day (3000 mg daily), for 2 months. Pouch endoscopy with biopsies was performed at the entry and at the end of the study. Results, According to the PDAI score, 8/11 patients (73%) improved their clinical condition and 7/11 (63%) were in remission at the end of the treatment. At 8 weeks, the median PDAI index decreased from 11.2 ± 2.3 to 6.6 ± 4.7 P < 0.01. No adverse events or toxicity were reported and all patients completed the study. Conclusions, Despite the limitations of the current study, sulfasalazine seems to be a potential treatment for acute pouchitis. Aliment Pharmacol Ther,31, 228,232 [source] SOMA (carisoprodol) toxicity in a dogJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 1 2005Stephen G. Lane DVM Abstract Objective: To describe a case of SOMA intoxication in a dog. Case summary: A 13-year-old, 25 kg, female spayed Australian shepherd presented to the emergency service after ingestion of ten to fifteen 350 mg tablets of SOMA (carisoprodol), a muscle relaxant used for back pain in humans. Toxic effects of the drug in this dog included mild sinus tachycardia, respiratory depression, seizures, and ataxia. The dog's mentation progressively deteriorated from depressed to comatose within 1 hour after admission. Treatment on initial presentation consisted of induction of emesis while the dog still had a gag reflex, administration of activated charcoal, oxygen therapy, and supportive care. The dog was discharged to the owner prior to full recovery (4 days later). New or unique information provided: This is the first known report of carisoprodol intoxication in the dog. [source] The feasibility of pain treatment at home after adenoidectomy with ketoprofen tablets in small childrenPEDIATRIC ANESTHESIA, Issue 5 2000Hannu Kokki MD In this study, we investigated the feasibility of pain treatment using ketoprofen 25 mg tablets (5 mg·kg,1·day,1) at home in children after daycase adenoidectomy. We also determined the adverse events and the incidence of postoperative bleeding during the first week after surgery. Initially, we studied 611 children aged 1,9 years. The study design was prospective, longitudinal, and open. The final data consisted of 555 (91%) children, and 522 children who received ketoprofen at home. The parents administered four (1,10, median with 10th and 90th percentiles) ketoprofen tablets to their children during the first week. A total of 20% of the parents experienced problems in administering tablets, and problems were three times more common in children under 48 months compared to older children. The main problems were swallowing difficulties and the unpleasant taste of the tablet. Neither serious adverse events, nor clinically significant bleeding occurred. Ketoprofen at the dose of 5 mg·kg,1·day,1 proved to be a safe analgesic in children for short-term use after adenoidectomy. [source] Bioequivalence evaluation of two brands of furosemide 40mg tablets (Salurin and Lasix) in healthy human volunteersBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2003Naji Najib Abstract A randomized, two-way, crossover, bioequivalence study was conducted in 24 fasting, healthy, male volunteers to compare two brands of furosemide 40 mg tablets, Salurin (Julphar, UAE) as test and Lasix (Hoechst AG, Germany) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in a joint venture with Al-Mowasah Hospital, Amman, Jordan. One tablet of either formulation was administered with 240 ml of water after a 10 h overnight fast. After dosing, serial blood samples were collected for a period of 12 h. Plasma harvested from blood was analysed for furosemide by a validated HPLC method. Various pharmacokinetic parameters including AUC0,t, AUC0,,, Cmax, Tmax, T1/2, and elimination rate constant were determined from plasma concentrations of both formulations. Statistical modules (ANOVA and 90% confidence intervals) were applied to AUC0,t, AUC0,,, and Cmax to assess the bioequivalence of the two brands which revealed no significant difference between them, and 90% CI fell within the US FDA accepted bioequivalence range of 80%,125%. Based on these statistical inferences, Salurin was found to be bioequivalent to Lasix. Copyright © 2003 John Wiley & Sons, Ltd. [source] Pharmacokinetics of tibolone in early and late postmenopausal womenBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2002C. J. Timmer Aims, Tibolone is a tissue-specific compound with favourable effects on bone, vagina, climacteric symptoms, mood and sexual well being in postmenopausal women, without stimulating the endometrium or breast. Since tibolone is used for the treatment of both young and elderly postmenopausal women, its pharmacokinetics were studied to investigate potential differences with age. In addition, the bioequivalence of the 1.25 and 2.5 mg tablets was evaluated. Methods, Single doses of 1.25 or 2.5 mg of tibolone were given in a double-blind, randomized, two-way cross-over study to women aged between 45 and 55 years or between 65 and 75 years of age. Results, Age did not have a significant effect on Cmax, tmax, and t½ of tibolone and its metabolites and on the body weight standardized oral clearance (CL/F kg,1) of the 3,- and 3,-hydroxy tibolones. In early postmenopausal women, significantly lower values were found for the AUC(0,16 h), and AUC(0,,) of 3,-hydroxy tibolone 24.6±6.6 vs 29.2±4.9 and 27.1±6.9 vs 32.3±6.5 ng ml,1 h for the 1.25 mg tablet, respectively, and 45.4±13.9 vs 55.7±14.1 and 49.6±14.6 vs 62.6±17.3 ng ml,1 h for the 2.5 mg tablet, respectively. When these values were adjusted for the significantly higher body weight of the early postmenopausal women, the differences disappeared. No significant differences between early and late postmenopausal women were found for the AUC(0,8 h), and AUC(0,,) of 3,-hydroxy tibolone. The rate of absorption of tibolone and the rates of absorption or formation of the 3,- and 3,-hydroxy tibolones were significantly higher after the 1.25 mg dose than after the 2.5 mg tablet, resulting in increases of 32%, 27% and 17% for the dose normalized- Cmax of tibolone and the 3,- and 3,-hydroxy tibolones, respectively. tmax for tibolone and its metabolites was 12,27% less after 1.25 mg compared to 2.5 mg, which was statistically significant. The two formulations were bioequivalent with respect to the dose-normalized AUC(0,,) and the AUC(0,tfix) values for the 3,-hydroxy tibolone (ratio point estimate [90%, confidence limits]: 1.08 [1.04, 1.14] and 1.08 [1.03, 1.13], respectively) and for the 3,-hydroxy tibolone (1.07 [1.01, 1.14] and 1.04 [0.96, 1.12], respectively). Both formulations were also bioequivalent with respect to CL/F kg,1 and t½. Conclusions, The pharmacokinetics of tibolone are similar in early (age 45,55 years) and late (65,75 years) postmenopausal women. The 2.5 and 1.25 mg tablets are bioequivalent with respect to the extent of absorption. The rate of absorption or formation of the metabolites of tibolone were not bioequivalent, but these differences are considered to have no clinical relevance in view of the chronic administration of tibolone. [source] Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trialACTA NEUROLOGICA SCANDINAVICA, Issue 2006D. L. Sparks Context,,, Recent evidence suggests that treatment of mild-to-moderate Alzheimer's disease (AD) with atorvastatin provides significant benefit on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) after 6 months. Objective,,, To determine if benefit on ADAS-cog performance produced by atorvastatin is influenced by severity of cognitive impairment, circulating cholesterol levels, or apolipoprotein E genotype. Design,,, A double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to atorvastatin calcium or placebo. Setting,,, A single-site study at the clinical research center of the Sun Health Research Institute. Participants,,, Ninety-eight individuals with mild-to-moderate AD (MMSE score of 12,28) provided informed consent, and 67 were randomized. Stable dose use of cholinesterase inhibitors, estrogen and vitamin E was allowed, as was the use of many other medications in the treatment of co-morbidities. Participants using cholesterol-lowering medications or being treated for major depression or a psychiatric condition were excluded. Intervention,,, Once daily atorvastatin calcium (80 mg; two 40 mg tablets) or placebo. Main outcome measures,,, A primary outcome measure was change ADAS-cog sub-scale score. Secondary outcome measures included scores on the MMSE, and circulating cholesterol levels. The Apolipoprotein E genotype was established for each participant. Results,,, A significant positive effect on ADAS-cog performance occurred after 6 months of atorvastatin therapy compared with placebo. This positive effect was more prominent among individuals entering the trial with, (i) higher MMSE scores, (ii) cholesterol levels above 200 mg/dl or (iii) if they harbored an apolipoprotein-E-4 allele compared with participants not responding to atorvastatin treatment. Individuals in the placebo group tended to experience more pronounced deterioration if their cholesterol levels exceeded 200 mg/dl or they harbored an apolipoprotein-E-4 allele. Conclusion,,, Atorvastatin therapy may be of benefit in the treatment of mild-to-moderately affected AD patients, but the level of benefit produced may be predicated on earlier treatment, an individual's apolipoprotein E genotype or whether the patient exhibits elevated cholesterol levels. [source] | |||||||||||||