Figure 1.

The first-pass metabolism of HIV drugs upon oral administration. After being swallowed, a drug is absorbed via the gut wall and intestine. It then enters the hepatic portal system. An abundance of drug metabolizing enzymes are present in the intestine and liver. Prior to metabolism, the drug is actively transported (OATPs = organic-anion-transporting peptides, OCTs = organic cation transporters, ABCs = ATP-binding cassette transporters, P-gp = P-glycoprotein, a member of ABCs) or passively diffuses into the cell, or both. In the liver, drug metabolism occurs inside hepatocytes where the drug undergoes modifications (e.g., oxidation by P450s) or conjugations (e.g., glucuronidation by UGTs). The resulting metabolites are excreted into the bile canaliculus or re-enter the blood, after which they can be excreted by the kidneys.