Administration of indinavir and low-dose ritonavir (800/100 mg twice daily) with food reduces nephrotoxic peak plasma levels of indinavir

• Published in: Antiviral therapy Vol. 8; no. 4; pp. 309 - 314
• Main Authors: AARNOUTSE, Rob E, WASMUTH, Jan-Christian, FÄTKENHEUER, Gerd, SCHNEIDER, Katrin, SCHMITZ, Karina, DE BOO, Theo M, REISS, Peter, HEKSTER, Yechiel A, BURGER, David M, ROCKSTROH, Jürgen K
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.08.2003
• Subjects: Adult; Biological and medical sciences; Cross-Over Studies; Drug Administration Schedule; Drug Therapy, Combination; Drug toxicity and drugs side effects treatment; Fasting; Food; Food-Drug Interactions; HIV Infections - drug therapy; HIV Infections - virology; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - adverse effects; HIV Protease Inhibitors - pharmacokinetics; HIV Protease Inhibitors - therapeutic use; Humans; Indinavir - administration & dosage; Indinavir - adverse effects; Indinavir - pharmacokinetics; Indinavir - therapeutic use; Kidney Diseases - chemically induced; Kidney Diseases - prevention & control; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Ritonavir - administration & dosage; Ritonavir - adverse effects; Ritonavir - pharmacokinetics; Ritonavir - therapeutic use; Toxicity: urogenital system; Biological fluid; Ritonavir; Meal; Food drug interaction; Blood plasma; Prevention; Antiviral; Indinavir; Kidney disease; Human; Immunopathology; Drug combination; Breakfast; Urinary system disease; Enzyme; Low dose; Enzyme inhibitor; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Peptidases; Chemotherapy; Treatment; Viral disease; Hydrolases; Human immunodeficiency virus; Pharmacokinetics; Nephrotoxicity; Protease inhibitor
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350300800407

The objective of this study was to compare indinavir peak plasma (Cmax) values after administration of indinavir/ritonavir 800/100 mg on an empty stomach or with food. High indinavir Cmax values have been associated with indinavir-related nephrotoxicity. This was an open-label, randomized, two-treatment, two-period, cross-over pharmacokinetic study performed at steady state. HIV-infected patients who had been using indinavir/ritonavir 800/100 mg twice daily for at least 4 weeks were randomized to take this combination with a light breakfast (two filled rolls and 130 ml of fluid) on a first study day, and without food on a second day, or in the reverse order. The pharmacokinetics of indinavir and ritonavir were assessed after plasma and urine sampling during 12 h. Data for nine patients were evaluated. Administration of indinavir/ritonavir 800/100 mg on an empty stomach resulted in a higher indinavir Cmax [geometric mean (GM) ratio - fasting/fed and 95% confidence interval (CI): 1.28 (1.08-1.52), P=0.01] and a trend to a shorter indinavir tmax (P=0.07) compared to administration with food. The mode of administration of indinavir/ritonavir did not affect plasma indinavir Cmax and AUC values, parameters that have been associated with the antiviral efficacy of indinavir, nor the urinary excretion of indinavir. Administration of indinavir/ritonavir 800/100 mg on an empty stomach results in a higher indinavir Cmax compared to ingestion with a light meal. Stated the other way round, intake with a light meal reduces indinavir Cmax, which probably reflects a food-induced delay in the absorption of indinavir. It is recommended to administer indinavir/ritonavir 800/100 mg with food, as a possible means to prevent indinavir-related nephrotoxicity in patients who start or continue with this regimen.