Drug metabolism and countertransport by P-gp. During absorption, drugs are metabolized by intestinal cytochrome P450. P-gp assists by pumping drug back into intestinal lumen. Drugs that evade intestinal metabolism enter portal blood and are subject to further biotransformation by hepatic cytochrome P450. Most drugs undergo phase I metabolism in which metabolites may be further conjugated or are directly eliminated by kidney. Small group of drugs may undergo phase II metabolism with no prior biotransformation. Modified with permission from Reference 2.