A LIMITED SAMPLING METHOD FOR THE ESTIMATION OF FLUNARIZINE AREA-UNDER-THE-CURVE (AUC) AND MAXIMUM PLASMA-CONCENTRATION (C-MAX)

A limited sampling model has been developed for flunarizine following a 30 mg oral dose in epileptic patients who were receiving phenytoin o r carbamazepine or both, to estimate the area under the curve (AUC) an d maximum plasma concentration (C-max). The model was developed using training data sets from 30, 20, 15, or 10 patients at one or two time points. The equations describing the models for AUC using two time poi nts (3 and 24 h) and C-max for the training data set of 30 subjects we re [GRAPHICS] The model was validated on 64 patients who received flun arizine orally. The model provided reasonably good estimates for both AUC and C-max. The mean predicted AUC of flunarizine was 1230 +/- 717 ng h mL(-1), whereas the observed AUC was 1203 +/- 900 ng h mL(-1). Th e bias of the prediction was 2% and precision was 28%. The mean predic ted C-max of flunarizine was 86 +/- 32 ng mL(-1) as compared to an obs erved mean C-max of 90 +/- 42 ng mL(-1). The bias and precision of the prediction were 4% and 24%, respectively. The method described here m ay be used to estimate AUC and C-max for flunarizine without detailed pharmacokinetic studies. (C) 1997 by John Wiley & Sons, Ltd.