Scientific Publications by FDA Staff
Drug Metabol Drug Interact 2012 Aug;27(3):157-64
Interspecies scaling of biliary excreted drugs: prediction of human clearance and volume of distribution.
BACKGROUND: Interspecies differences in biliary excretion and the differences in bile flow rates make scaling across species difficult for drugs that are excreted in the bile. The objective of this study is to predict clearance (CL) and volume of distribution (V) for humans from animals for drugs that are excreted in the bile. METHODS: Clearance values of 10 drugs known to be excreted in the bile were selected from the literature. Scaling of CL was performed using at least three animal species. Using simple allometry and the rule of exponents (ROE), clearances of studied drugs were predicted in humans. Besides using the ROE, a 'correction factor' was applied adjusting bile flow rate based on the species body weight (bile flow mL/day/kg body weight) or liver weight (bile flow mL/day/kg liver weight). Using the ROE and combining it with the 'correction factor', the clearances of biliary excreted drugs were predicted for humans. V for 15 drugs (without any correction factor) that are excreted in the bile was also predicted for humans. RESULTS: The results of the study indicated that the ROE in association with the correction factors developed for the biliary excreted drugs substantially improved the prediction of human clearance for drugs that are excreted in the bile. In this study, there was no indication (unlike clearance) that the prediction of volume of drug distribution was affected (systematically under- or over-prediction) because of biliary excretion. CONCLUSIONS: The clearance of drugs that are excreted in the bile can be predicted with reasonable accuracy using ROE and a correction factor.
|Category: Journal Article|
|PubMed ID: #23092793||DOI: 10.1515/dmdi-2012-0012|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2012-12-10|