Abstract
From a search of the available literature, a database of twenty two drugs of all charge types and several different therapeutic classes was compiled in order to compare rat and human biliary clearance data. Dog biliary excretion data was also found for nine of the drugs. For nineteen of the twenty two drugs (86%), rat unbound biliary clearance values, when normalized for body weight, exceeded those for man by factors ranging from 9 to over 2500-fold, whereas human/dog differences were much less dramatic. It was possible to define hepatic uptake and efflux transporter involvement for many of the drugs. Based on the findings it is postulated that regardless of the biliary efflux transporters implicated, when drugs do not require active hepatic uptake to access the liver there may be fairly insignificant differences in rat, dog and human biliary clearance. Conversely, when the organic anion-transporting polypeptide drug transporters are involved, one may expect at least a ten-fold discrepancy in rat to human biliary clearance normalized for body weight and corrected for plasma protein binding.
- active transport
- biliary excretion
- drug clearance
- hepatic transport
- hepatic uptake
- hepatobiliary disposition
- hepatobiliary transport
- transporters
- Received October 3, 2012.
- Accepted November 8, 2012.
- The American Society for Pharmacology and Experimental Therapeutics