EVALUATION OF COVARIATES INFLUENCE ON EUPRESSYL PHARMACOKINETICS USING LINEAR REGRESSION MODEL

Abstract

The identification and quantification of covariates, particularly using population pharmacokinetics is now seen as an integral part of drug development. This present study was aimed to assess the influence of subject specific parameters (covariates) on pharmacokinetics of Eupressyl (Urapidil) from typical pharmacokinetics studies. The influence of covariates (age, height, body weight, body mass index) on the pharmacokinetics of Urapidil was evaluated analyzing the data pooled from three different pharmacokinetic studies. The influence of covariates on Urapidil pharmacokinetics was evaluated using linear mixed effect model. Covariate analysis was carried out following a two-stage approach. Results from the first stage analyses showed that there is no significant effect (P > 0.05) on Urapidil pharmacokinetic parameters against evaluated covariates. However, at second stage following linear mixed effect models, subject specific parameters were correlated with obtained pharmacokinetic parameters. The results evidencing that the reasonable influence of covariates on Urapidil pharmacokinetics parameters were observed for different lot of innovator products. Thus, characterizing effect of few of the covariates on pharmacokinetics outcome will definitely reduce the number of pharmacokinetic studies using healthy human subjects and also development time and cost in generic drug developments. However, further pharmacokinetic models for Urapidil to be developed and validated using non-linear mixed effectmodels, as it is considered one of the standard method for evaluating drug variability.