Farmacocinética de poblaciÓn del valproato: influencia de la dosis y la comedicaciÓn

Routine clinical pharmacokinetic data collected from patients receiving valproic acid (VPA) wore analyzed to estimate population pharmacokinetic parameters. The data were 77 steady-state VPA concentrations and associated dosage in 25 patients. The data were analyzed using NONMEM, a computer program designed for population pharmacokinetic analysis. A log-normal distribution model was used to examine the influence of the interindividual variance, the effect of the dose and the influence of polytherapy on the population mean value of VPA apparent clearance (Clap). The In Clap were estimated to be 2.92 mL/min. Significant intersubject effect was found. Clap is not influenced by daily dose. The Clap of VPA is higher when the drug is given in combination with other antiepileptic drugs. Our log-linear model gives accurate estimates of pharmacokinetic parameters, and a significant interindividual variability.