A LIMITED SAMPLING METHOD FOR THE ESTIMATION OF AUC AND C-MAX OF CARBAMAZEPINE AND CARBAMAZEPINE EPOXIDE FOLLOWING A SINGLE AND MULTIPLE-DOSE OF A SUSTAINED-RELEASE PRODUCT

Aims The objectives of this study are to develop a model to predict ar ea under the curve (AUG) and maximum plasma concentration (C-max) of c arbamazepine (CBZ) and its active metabolite carbamazepine epoxide (CB ZE) following single and multiple dose of CBZ using one or mio samples in volunteers. Methods Limited sampling models (LSM) were developed f or CBZ and CBZE following 200-800 mg single oral dose and 400-800 mg t wice daily dose for 14 days of a sustained-release product (CBZ-SR) to estimate AUC and C-max. The LSM was developed from a training data se t of 15 subjects using one blood sample taken at 48 h following a sing le dose. The model was validated on 60 subjects who received different doses of CBZ. Following multiple dosing, the LSM was developed from a training data set of 10 subjects using the steady state C-min (plasma concentration obtained 5 min before the last CBZ-SR dose). Results Th e model provided good estimates of AUC and C-max for CBZ and CBZE. The bias and the precision of the predicted AUC and C-max for CBZ and CBZ E were less than 10% and 15%, respectively. Similar results were obtai ned when CBZ was given as multiple dose. Conclusions The method descri bed here may be used to estimate AUC and C-max for CBZ and CBZE withou t detailed pharmacokinetic studies following single or multiple dose o f CBZ.