PHARMACOKINETIC PARAMETERS OF VALPROIC ACID AND CARBAMAZEPINE FROM ROUTINELY COLLECTED DATA: INFLUENCE OF PATIENT CHARACTERISTICS

Individualising a drug dosage regimen is more appropriate if it is based on pharmacokinetics data derived from local populations. In this study, we estimated valproic acid (VPA) and carbamazepine (CBZ) clearances in the Malaysian population from routinely collected therapeutic drug monitoring (TDM) data. We also evaluated the effects of gender, age, weight and concurrent antiepileptic drug (AED) therapy on VPA and CBZ clearance. Data was collected retrospectively from TDM forms of adult patients. Apparent drug clearance was estimated based on the standard steady state clearance equation. Mann-Whitney and Kruskal-Wallis tests were used to evaluate gender and therapy differences, while Spearman’s Rank correlation was used to determine the associations of age and weight with clearance. One hundred thirty-two samples for VPA and 67 for CBZ were included in the analysis. Patients’ ages ranged from 15 to 72 years old. Mean VPA and CBZ clearances were found to be 0.36 l/kg/d and 1.60 l/kg/d, respectively. VPA clearance correlated positively but poorly with weight. Our results showed significant differences in (i) VPA clearance among male and female patients and (ii) VPA clearance between monotherapy and combination therapy. These findings provide a guide to initiate maintenance doses of VPA and CBZ in our local patients. Awareness of factors influencing drug clearance should help to optimise patients’ dosing regimens.