Effects of Grapefruit Juice on Pharmacokinetic Exposure to Indinavir in HIV-Positive Subjects

• Published in: Journal of clinical pharmacology 2001-04, Vol.41 (4), p.435-442
• Main Authors: Shelton, Mark J., Wynn, Heather E., Hewitt, Ross G., DiFrancesco, Robin
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Beverages; Biological and medical sciences; Biological Availability; Chromatography, High Pressure Liquid; Citrus; Cross-Over Studies; Female; Food-Drug Interactions; Gastric Juice - metabolism; Half-Life; HIV Infections - drug therapy; HIV Infections - metabolism; Humans; Hydrogen-Ion Concentration; Indinavir - pharmacokinetics; Indinavir - pharmacology; Male; Medical sciences; Middle Aged; Models, Biological; Pharmacology. Drug treatments; Time Factors
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/00912700122010140

The objective of this study was to determine the effects of double‐strength grapefruit juice on gastric pH and systemic bioavailability of indinavir in HIV‐infected subjects receiving indinavir. Fourteen HIV‐infected subjects took 800 mg of indinavir with 6 ounces (180 ml) of water or double‐strength grapefruit juice. Gastric pH was measured and blood samples were collected for 5 hours after indinavir dosing. Grapefruit juice increased the mean gastric pH (from 1.39 ± 0.4 to 3.20 ± 0.3; p < 0.05) and slightly delayed the absorption of indinavir (tmax increased from 1.12 ± 0.8hto 1.56± 0.6 h; p < 0.05). However, there were no significant differences in indinavir exposure. Cmax was 16.7 ± 7.3 μ with water versus 13.9 ± 4.2 μ with grapefruit juice (p = NS), and AUC0–8 was 37.5 ± 19 with water versus 36.9 ± 15 with grapefruit juice (p = NS). The authors concluded that concomitant administration of grapefruit juice increases gastric pH and delays indinavir absorption but does not uniformly affect the systemic bioavailability of indinavir in HIV‐infected subjects.