Quinidine pharmacokinetics in man Choice of a dis

Authors: Theodor W Guentert Nicholas H G Holford Peter E Coafes Robert A Upton Sidney Riegelman

Publish Date: 2015/07/17

Volume: 7, Issue: 4, Pages: 315-330

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Abstract

Parameters describing disposition and absolute oral bioavailability of quinidine were determined in ten normal male volunteers using a specific assay Various models were compared for their ability to describe the experimental data An intravenous quinidine gluconate and an oral quinidine sulfate solution were administered 374 mg/kg quinidine base In three subjects the intravenous and oral studies were repeated One two and threecompartment models with zeroand firstorder input were fitted to the plasma concentrations The selection of the best model was made by the Akaike information criterion and by eye After intravenous administration plasma concentrationtime curves could be adequately described by a twocompartment model Mean disposition constants ±SD were obtained from individualized fits V1 0398 ±0336 liter/kg Vdarea 253±072 liter/kg α 0316±0294 min−1 Β 000204 ± 000262 min1 k2 00305 ±0010 min−1 A clearance of 49 ±15 ml/min/kg was observed After oral administration threecompartment models were needed to describe the observed data in some cases Absorption was in most cases best described by a zeroorder rather than by a firstorder process The time to peak concentration varied from 23 to 121 min the lag time was always less than 3 min and the mean elimination rate constant was 000171 min−1 The mean oral bioavailability of quinidine was 070 ±017This study was supported by funds from Food and Drug Administration Contract No 223743145 T W G acknowledges support from the Swiss National Science Foundation N H G H received a NIH fellowship for training in Clinical Pharmacology GM 00001

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