Premium
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
Author(s) -
Mahmood Iftekhar,
Chamberlin Nancy
Publication year - 1998
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1998.00668.x
Subject(s) - carbamazepine , pharmacokinetics , anticonvulsant , pharmacology , metabolite , dosing , chemistry , area under the curve , blood sampling , medicine , epilepsy , biochemistry , psychiatry
Aims The objectives of this study are to develop a model to predict area under the curve (AUC) and maximum plasma concentration ( C max ) of carbamazepine (CBZ) and its active metabolite carbamazepine epoxide (CBZE) following single and multiple dose of CBZ using one or two samples in volunteers.Methods Limited sampling models (LSM) were developed for CBZ and CBZE following 200–800 mg single oral dose and 400–800 mg twice 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 set of 15 subjects using one blood sample taken at 48 h following a single 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 The 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 CBZE were less than 10% and 15%, respectively. Similar results were obtained when CBZ was given as multiple dose.Conclusions The method described here may be used to estimate AUC and C max for CBZ and CBZE without detailed pharmacokinetic studies following single or multiple dose of CBZ.