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Steady-state Plasma Concentrations (steady-state + plasma_concentration)
Selected AbstractsPlasma Concentrations of Risperidone and Olanzapine during Coadministration with OxcarbazepineEPILEPSIA, Issue 5 2005Maria Rosaria Muscatello Summary:,Purpose: Oxcarbazepine (OZC) is a second-generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P-450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. Methods: OXC, at a dosage of 900,1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2,6 mg/day) and 13 on olanzapine (5,20 mg/day). Steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by high-pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. Results: OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 ± 3.6 ng/ml at baseline to 4.8 ± 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6 ± 7.5 to 24.7 ± 7.4 ng/ml), and olanzapine (from 26.5 ± 5.7 ng/ml at baseline to 27.8 ± 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. Conclusions: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug-metabolizing enzymes. [source] Correlation between scores on Continuous Performance Test and plasma concentration for schizophrenic patients on risperidonePSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2004PO SEE CHEN md Abstract, The purpose of the present paper was to evaluate the relationship between plasma antipsychotics concentration and cognitive task performance. This may provide valuable information for rational dosage titration. Literature on the relationship between plasma risperidone (RIS) concentration and performance on the Continuous Performance Test (CPT) remains scarce. Ten patients (four male, six female) were given RIS for more than 1 year. Steady-state plasma concentrations of the parent drug RIS and its active metabolite, 9-hydroxy-risperidone (9-OH-RIS), were measured using specific liquid chromatography-tandem mass spectrometry assay. Psychopathology, side-effects of extrapyramidal symptoms (EPS) and CPT were also assessed. A negative correlation was found between CPT performance and the plasma RIS, 9-OH-RIS and its active moiety (RIS + 9-OH-RIS) concentrations. Both RIS and 9-OH-RIS have an impact on the CPT performance of schizophrenic patients. Optimal active moiety plasma concentration for best cognitive performance needs further study. [source] Pharmacodynamic Analysis of the Interaction between Tiagabine and Midazolam with an Allosteric Model That Incorporates Signal TransductionEPILEPSIA, Issue 3 2003Daniël M. Jonker Summary: ,Purpose: The objective of this study was to characterize quantitatively the pharmacodynamic interaction between midazolam (MDL), an allosteric modulator of the ,-aminobutyric acid subtype A (GABAA) receptor, and tiagabine (TGB), an inhibitor of synaptic GABA uptake. Methods: The in vivo concentration,response relation of TGB was determined through pharmacokinetic/pharmacodynamic (PK/PD) modeling. Rats received a single intravenous dose of 10 mg/kg TGB in the absence and the presence of a steady-state plasma concentration of MDL. The EEG response in the 11.5- to 30-Hz frequency band was used as the pharmacodynamic end point. Results: Infusion of MDL resulted in a mean steady-state plasma concentration of 66 ± 3 ng/ml. A significant pharmacokinetic interaction with TGB was observed. MDL inhibited TGB clearance by 20 ± 7 ml/min/kg from the original value of 89 ± 6 ml/min/kg. However, no changes in plasma protein binding of both drugs were observed. The concentration,EEG relation of TGB was described by the sigmoid- Emax model. The pharmacodynamic parameter estimates of TGB were: Emax = 327 ± 10 ,V, EC50 = 392 ± 20 ng/ml, and nH = 3.1 ± 0.3. These values were not significantly different in the presence of MDL. Factors that may explain the lack of synergism were identified by a mechanism-based interaction model that separates the receptor activation from the signal-transduction process. High efficiency of signal transduction and the presence of a baseline response were shown to diminish the degree of synergism. Conclusions: We conclude that the in vivo pharmacodynamic interaction between MDL and TGB is additive rather than synergistic. This strongly suggests that allosteric modulation of the antiseizure activity of a GAT-1 inhibitor by a benzodiazepine does not offer a therapeutic advantage. [source] Once-daily nevirapine dosing: a pharmacokinetics, efficacy and safety reviewHIV MEDICINE, Issue 1 2007CL Cooper In the context of attempts to simplify treatment regimens and enhance adherence, there is great interest in once-daily dosing regimens for the treatment of HIV-1 infection. Nevirapine has a long half-life and achieves high steady-state plasma concentrations relative to the concentration required to inhibit 50% viral replication in vitro (IC50) in patients. For this reason, it has been considered as a once-daily antiretroviral. Pharmacokinetic and efficacy data support the use of this dosing approach, but excess rash and lingering concerns over liver toxicity preclude use of once-daily dosed nevirapine at this time. Tolerance to high nevirapine concentrations may develop when dose escalation is used during initiation of therapy. It is theoretically possible that the benefits of once-daily dosing may be achieved without excess toxicity by switching to once-daily nevirapine following several months of twice-daily administration. This dosing strategy is currently under evaluation. [source] No pharmacokinetic interaction between paliperidone extended-release tablets and trimethoprim in healthy subjects,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2009An Thyssen Abstract Objective The effect of trimethoprim, a potent organic cation transport inhibitor, on the pharmacokinetics (PK) of paliperidone extended-release tablets (paliperidone ER), an organic cation mainly eliminated via renal excretion, was assessed. Methods Open-label, two-period, randomized, crossover study in 30 healthy males. Single dose of paliperidone ER 6,mg was administered either alone on day 1 or day 5 during an 8-day treatment period of trimethoprim 200,mg twice daily. Serial blood and urine samples were collected for PK and plasma protein binding of paliperidone and its enantiomers. The 90% confidence interval (CI) of ratios with/without trimethoprim for PK parameters of paliperidone and its enantiomers calculated. Results Creatinine clearance decreased from 119 to 102,mL,min,1 with trimethoprim. Addition of trimethoprim increased unbound fraction of paliperidone by 16%, renal clearance by 13%, AUC, by 9%, and t½ by 19%. The 90% CIs for ratios with/without trimethoprim were within the 80,125% range for Cmax, AUClast, and renal clearance. For AUC,, 90% CI was 79.37,101.51, marginally below the lower bound of the acceptance range. Paliperidone did not affect steady-state plasma concentrations of trimethoprim. Conclusions No clinically important drug interactions are expected when paliperidone ER is administered with organic cation transport inhibitors. Copyright © 2009 John Wiley & Sons, Ltd. [source] Comparative Cerebrospinal Fluid Diffusion of Imipenem and Meropenem in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2000ANTOINE DUPUIS The main objective of this study was to compare the cerebrospinal fluid (CSF) diffusion of imipenem and meropenem at steady state, following intravenous infusions at various rates in rats. A preliminary experiment was conducted to estimate the elimination half-lives of these two carbapenem antibiotics, and then to evaluate the infusion duration necessary to reach steady state. CSF diffusion of imipenem was essentially linear over the wide range of infusion rates (66,1320 ,g min,1) and corresponding steady-state plasma concentrations (11.7,443.0 ,g mL,1). Conversely the CSF diffusion of meropenem was saturable, with a predicted maximum CSF concentration equal to 1.3 ,g mL,1. Extrapolation of these data to the clinical situation may not be possible since the rats had normal blood-brain and blood-CSF barriers whereas patients with diseases such as meningitis may not. However, it is suggested that the observed differences in the diffusion characteristics of imipenem and meropenem may be partly responsible for their differences in toxicity and efficacy at the central level. [source] | ||||||||||