Perifusion Model for Detoxification of Drugs in a Bioartificial Liver

Abstract

Detoxification of a drug in a bioartificial liver (BAL) during an in vitro experiment was theoretically carried out based on a perifusion model. The detoxification capacity assay, the rates of disappearance of the chemicals such as flow-limited and enzyme-limited drugs in the BAL system could be defined from models of hepatic perfusion-elimination relationships. When the flow-limited drug administrated under a quasi-equilibrium condition, a two-compartment model for the concentration behavior of the drug was introduced and compared with a one-compartment model. For both models, equations involving hepatic drug clearance and various pharmacokinetic parameters were derived under initial bolus loading and constant-rate infusion plus bolus loading conditions. The concentration of enzyme-limited drug in the BAL decreased linearly with time in contrast with the concentration profile of the flow-limited drug followed by exponential functions. The perifusion model offers a quantitative understanding of the elimination kinetics of chemicals such as flow-limited and enzyme-limited drugs in a bioartificial liver and a comparison between the BAL and human liver.