Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects.
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 +/- 0.8 h to 1.56 +/- 0.6 h; p < 0.05). However, there were no significant differences in indinavir exposure. Cmax was 16.7 +/- 7.3 microM with water versus 13.9 +/- 4.2 microM 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.
Shelton
M J
MJ
Antiviral Clinical Pharmacology Unit, Immunodeficiency Services Clinic of Erie County Medical Center, 462 Grider Street, Buffalo, NY 14215, USA.
Wynn
H E
HE
Hewitt
R G
RG
DiFrancesco
R
R
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001628:Beverages; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D002957:Citrus; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D005750:Gastric Juice / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019469:Indinavir / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D013997:Time Factors
D019380:Anti-HIV Agents; D019469:Indinavir