Population pharmacokinetic studies of various drugs used in CNS related diseases in south Indian patients

Abstract

x newlineABSTRACT newlineAIMS newlineTo characterize pharmacokinetic (PK) variability of risperidone and 9-OH risperidone newlineusing sparse sampling and to evaluate the effect of covariates on PK parameters. newlineMETHODS newlinePK analysis used plasma samples collected from the Clinical Anti-psychotic Trials of newlineIntervention Effectiveness. A nonlinear mixed-effects model was developed using newlineNONMEM to describe simultaneously the risperidone and 9-OH risperidone newlineconcentration time profile. Covariate effects on risperidone and 9-OH risperidone PK newlineparameters were assessed, including age, weight, sex, smoking status, race and newlineconcomitant medications. newlineRESULTS newlinePK samples comprised risperidone and 9-OH risperidone concentrations from 20 newlinesubjects that were available for analysis. Ages ranged from 18 to 93 years. Population newlinePK submodels for both risperidone and 9-OH risperidone with first-order absorption newlinewere selected to describe the concentration time profile of risperidone and 9-OH newlinerisperidone. A mixture model was incorporated with risperidone clearance (CL) newlineseparately estimated for three subpopulations [poor metabolizer (PM), extensive newlinemetabolizer (EM) and intermediate metabolizer (IM)]. Age significantly affected 9-OH newlinerisperidone clearance. Population parameter estimates for CL in PM, IM and EM were newline12.9, 36 and 65.4 l h-1 and parameter estimates for risperidone half-life in PM, IM and newlineEM were 25, 8.5 and 4.7 h, respectively. newlineCONCLUSIONS newlineA one-compartment mixture model with first-order absorption adequately described newlinethe risperidone and 9-OH risperidone concentrations. Age was identified as a newlinesignificant covariate on 9-OH risperidone clearance in this study. newline