Abstracts

The objective of this study was to characterize the pharmacokinetic profile of carbamazepine (CBZ) in adult Saudi epileptic patients in order to improve on dosing schedules., One hundred and fifty two steady- state serum CBZ concentration measurements were collected during normal routine care of 76 patients receiving CBZ (100-1000 mg/day) in monotherapy. Steady- state trough CBZ serum concentrations, CBZ dosing history and associated information were collected prospectively. Data were analyzed by the non- linear mixed- effect modeling (NONMEM) technique with a one- compartmental model of first- order absorption and elimination. The apparent clearance (CL/F) and apparent volume of distribution (V/F) and their inter-individual variabilities were estimated using the program., The population estimates for clearance (CL; modeled independently of dose) and volume of distribution were 12.6[plusmn]0.5 l/h and 535[plusmn]40 l, respectively. However, CL increased as a function of dosing rate and consequently was modeled as a linear function of steady- state concentration. In order to validate these results, the predictions of the population model were tested against data from 14 further patients subjected to the same inclusion criteria but who were not included in the original analysis. The predictions were good, being unbiased (p=0.29), and had an average deviation from the observed values of 16%., The observed covariate regression model reasonably predicted concentrations in the separate validation Saudi patient data set. The correlation between CBZ clearance and patient- specific characteristics may thus allow dosage adjustment to be made to achieve target steady- state plasma concentrations., (Supported by: This study was funded by King Saud University (KSU), Riyadh, Saudi Arabia. Ethical clearance permission to conduct this study was obtained from the Ethics Committee of the College of Medicine, KSU and written consent was obtained from all patients.)