ISSN:
1573-8744
Keywords:
quinidine
;
pharmacokinetic models
;
curve fitting
;
bioavalability
;
absorption
;
humans
;
plasma
;
intravenous
;
oral
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
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 (3.74 mg/kg quinidine base). In three subjects the intravenous and oral studies were repeated. One-, two-, and three-compartment models with zeroand first-order 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: 0.398 ±0.336 liter/kg, Vdarea: 2.53±0.72 liter/kg, α: 0.316±0.294 min−1, Β: 0.00204 ± 0.00262 min1, k2: 0.0305 ±0.010 min−1). A clearance of 4.9 ±1.5 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 0.00171 min−1. The mean oral bioavailability of quinidine was 0.70 ±0.17.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01062532
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