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A LIMITED SAMPLING METHOD FOR THE ESTIMATION OF FLUNARIZINE AREA UNDER THE CURVE (AUC) AND MAXIMUM PLASMA CONCENTRATION ( C MAX )
Author(s) -
MAHMOOD IFTEKHAR,
SAHLROOT J. TODD
Publication year - 1997
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199703)18:2<117::aid-bdd5>3.0.co;2-c
Subject(s) - cmax , flunarizine , pharmacokinetics , area under the curve , carbamazepine , plasma concentration , mathematics , chemistry , pharmacology , medicine , epilepsy , psychiatry , calcium
A limited sampling model has been developed for flunarizine following a 30 mg oral dose in epileptic patients who were receiving phenytoin or carbamazepine or both, to estimate the area under the curve (AUC) and 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 points (3 and 24 h) and C max for the training data set of 30 subjects were AUC predicted =11·1 C 3 h +121·4 C 24 h –157 ( r =0·80) C max(predicted) =0·036 AUC+42·9 ( r =0·74) The model was validated on 64 patients who received flunarizine 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 . The bias of the prediction was 2% and precision was 28%. The mean predicted C max of flunarizine was 86±32 ng mL −1 as compared to an observed 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 may be used to estimate AUC and C max for flunarizine without detailed pharmacokinetic studies. © 1997 by John Wiley & Sons, Ltd.