Pharmacokinetic modeling of the hepatobiliary transport mediated by cooperation of uptake and efflux transporters.
Hepatocytes express various transporters in the sinusoidal and canalicular membrane, which mediate hepatic uptake and canalicular efflux, forming directional transport from the sinusoid to the bile. Drug-drug interactions and genetic polymorphisms of the transporters are known to cause variations in transporter function. This review focuses on pharmacokinetic modeling of hepatobiliary transport of drugs to explain the alteration of the disposition of drugs caused by such variations, based on the clearance concept. For modeling and simulation, pravastatin and dibromosulfophthalein have been used as model compounds which are known to undergo transpoter-mediated hepatic uptake followed by biliary excretion. Pharmacokinetic modeling of hepatobiliary transport illustrates the concept of the rate-determining process in overall hepatobiliary transport.
Kusuhara
Hiroyuki
H
The University of Tokyo, Japan.
Sugiyama
Yuichi
Y
D000465:Algorithms; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics
D002352:Carrier Proteins; D004364:Pharmaceutical Preparations