A method for estimating within-individual variability in clearance and in volume of distribution from standard bioavailability studies |
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Authors: | Robert A. Upton Jean-Francois Thiercelin John K. Moore Sidney Riegelman |
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Affiliation: | (1) Department of Pharmacy, University of California, 94143 San Francisco, California;(2) Laboratoires d'Études et de Recherches Synthelabo, 58 Rue de la Glacière, 75013 Paris, France;(3) Department of Laboratory Medicine, University of California, 94143 San Francisco, California |
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Abstract: | Bioavailability studies are commonly undertaken, and most, because they involve subjects taking repeated doses of a drug, contain information on intraindividual variability in pharmacokinetics. However, because in such studies bioavailability itself is unknown, it is difficult to resolve which pharmacokinetic parameters vary within individuals. A mathematical model is presented which permits estimation of variability in clearance and in volume of distribution. When applied to pooled data arising from five theophylline bioavailability studies, this model has given statistical evidence that clearance of theophylline is inherently more variable within individuals (coefficient of variation, 13%) than volume of distribution (8%). As a result, use of the measurement AUC · rather than AUCas a more precise index of bioavailability is justified in studies where is measured with reasonable precision. The model could be applied to estimation of withinbatch within-person variability in bioavailability.Deceased, April 4th, 1981. |
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Keywords: | theophylline intraindividual variability within-individual variability clearance volume |
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