Interspecies scaling of renally secreted drugs.
The objective of this study is to predict pharmacokinetic parameters (clearance, volume of distribution at steady state, and elimination half-life) in humans from animal data for drugs which are renally secreted in humans. Pharmacokinetic parameters of ten drugs were scaled-up from animal data obtained from the literature. Using simple allometry (pharmacokinetic parameter of interest vs body weight), total, renal and nonrenal clearances, volume of distribution and half-life were predicted in humans. The predicted parameters were compared with the observed parameters. The results of the study indicated that it is likely that the predicted total and renal clearances from animal data will be underestimated in humans for renally secreted drugs. The prediction of renal clearance was improved by normalizing the renal clearance by a 'correction factor' for animals who exhibited renal secretion. The predicted volume and half-life were comparable with the observed values in man. Overall, the results of this study indicate that caution should be employed in interpreting the total and renal clearance of renally secreted drugs predicted by the allometric approach.
Mahmood
I
I
Office of Clinical Pharmacology and Biopharmaceutics, HFD-860, Food & Drug Administration, Rockville, MD 20852, USA.
D000818:Animals; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D013045:Species Specificity