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Hepatic drug metabolism is a major route of drug elimination, mediated by multiple drug-metabolizing enzymes. Any changes in the rate and extent of hepatic drug metabolism can lead to altered drug efficacy or toxicity. Accumulating clinical evidence indicates that pregnancy is accompanied by changes in hepatic drug metabolism. In this article, we discuss in vitro and in vivo tools used to study the mechanisms underlying the altered drug metabolism during pregnancy, focusing on primary hepatocyte culture, transgenic animal models, and use