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  • Title: Prediction of the disposition of nine weakly acidic and six weakly basic drugs in humans from pharmacokinetic parameters in rats.
    Author: Sawada Y, Hanano M, Sugiyama Y, Iga T.
    Journal: J Pharmacokinet Biopharm; 1985 Oct; 13(5):477-92. PubMed ID: 3938813.
    Abstract:
    Various pharmacokinetic parameters--disposition half-life, t1/2,z, metabolic clearance CLm, volume of distribution V, intrinsic clearance of unbound drug CLuint, and unbound volume of distribution of tissues (distributive tissue volume/fraction of drug in tissue unbound, VT/fuT--are compared in rat and human for nine weakly acidic drugs, phenytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, and amobarbital, and six weakly basic drugs, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam. With regard to all parameters, statistically significant correlations are obtained when parameters are plotted on a log-log plot. Correlation coefficients between the intrinsic parameters (CLuint or VT/fuT) were higher than those between the hybrid parameters (t1/2,z, CLm or V). In general, these drugs were metabolized ten times more rapidly in rat than in human. With regard to the tissue distribution of these drugs, there was little difference between rat and human. Predictions of CLm, V, and t1/2, in humans using rat data were successful for most drugs, with a few marked exceptions.
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