Indinavir

It is well absorbed orally and, of all the protease inhibitors, is the least protein bound, at 60 percent. Acidic gastric conditions are necessary for absorption. Absorption is decreased when administered with meals, although a light, low-fat snack is permissible. Ritonavir overcomes this problem and also permits twice-a-day dosing. Metabolism and hepatic clearance account for elimination of indinavir. The dosage should, therefore, be reduced in the presence of hepatic insufficiency. Indinavir has the shortest half-life of the protease inhibitors, at 1.8 hours. It is well tolerated, with the usual GI symptoms and headache predominating. Indinavir characteristically causes nephrolithiasis and hyperbilirubinemia. Adequate hydration is important to reduce the incidence of kidney stone formation, and patients should drink at least 1.5 L of water per day. Fat redistribution is particularly troublesome with this drug.nausea, diarrhea, thrombocytopenia, To reduce renal damage, it is important to maintain good hydration. Insulin resistance may be more common with indinavir than other PIs. Indinavir is a substrate for and an inhibitor of the cytochrome P450 isoform CYP3A4 and is implicated in drug interactions. Serum levels of indinavir are increased by azole antifungals and decreased by rifamycins. Indinavir increases the serum levels of antihistamines, benzodiazepines, and rifampin.