Saquinavir

To maximize bioavailability, saquinavir is always given along with a low dose of ritonavir. High-fat meals also enhance absorption. Elimination of saquinavir is primarily by metabolism, followed by biliary excretion. Its half-life is 7 to 12 hours, requiring twice daily doses. Drugs that enhance the metabolism of saquinavir, such as rifampin, rifabutin, nevirapine, efavirenz, and other enzyme inducers, should be avoided if possible. The most common adverse effects of saquinavir treatment include headache, fatigue, dyspepsia rhinitis diarrhea, nausea, and other GI disturbances. Increased levels of hepatic aminotransferases have been noted, particularly in patients with concurrent viral hepatitis B or C infections.Original formulations of saquinavir had low and erratic oral bioavailability. Reformulation for once-daily dosing in combination with low-dose ritonavir has improved efficacy with decreased GI side effects. The drug undergoes extensive first-pass metabolism and functions as both a substrate and inhibitor of CYP3A4.Saquinavir plasma levels are increased by azole antifungals, clarithromycin, grapefruit juice, indinavir, and ritonavir. Drugs that induce CYP3A4 decrease plasma levels of saquinavir.