TY - JOUR
T1 - Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics
AU - Penzak, Scott Robert
AU - Acosta, Edward P.
AU - Turner, Michele
AU - Edwards, David J.
AU - Hon, Yuen Yi
AU - Desai, Hiral D.
AU - Jann, Michael W.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Considerable interpatient variability in indinavir pharmacokinetics, possibly due in part to variable metabolism of the drug through intestinal cytochrome P450 (CYP) 3A4, may contribute to poor virologic response in certain individuals with HIV infection. The purpose of this study was to characterize the influence of intestinal CYP3A4 modulation with grapefruit juice and Seville orange juice on indinavir pharmacokinetics. In an open-label, three-period crossover study, 13 healthy volunteers received indinavir 800 mg every 8 hours for 1 day and a single 800 mg dose the next morning. The last two indinavir doses were taken with 8 ounces of Seville orange juice, single-strength grapefruit juice, or water (control). Plasma samples were collected at time 0 (predose) and at 0.5, 1, 2, 3, 4, and 5 hours after the last indinavir dose. Concentration-time data were analyzed using noncompartmental methods. Coadministration of Seville orange juice and indinavir resulted in a statistically significant increase in indinavir tmax (1.87 [1.65-2.22] vs. 1.25 [1.03-1.60] h; p < 0.05) without altering other pharmacokinetic parameter values. Grapefruit juice administration did not result in any changes in indinavir pharmacokinetics. Modulation of intestinal CYP3A4 by grapefruit juice and Seville orange juice did not alter the systemic availability of indinavir. The contribution of presystemic metabolism to indinavir interpatient variability appears to be small.
AB - Considerable interpatient variability in indinavir pharmacokinetics, possibly due in part to variable metabolism of the drug through intestinal cytochrome P450 (CYP) 3A4, may contribute to poor virologic response in certain individuals with HIV infection. The purpose of this study was to characterize the influence of intestinal CYP3A4 modulation with grapefruit juice and Seville orange juice on indinavir pharmacokinetics. In an open-label, three-period crossover study, 13 healthy volunteers received indinavir 800 mg every 8 hours for 1 day and a single 800 mg dose the next morning. The last two indinavir doses were taken with 8 ounces of Seville orange juice, single-strength grapefruit juice, or water (control). Plasma samples were collected at time 0 (predose) and at 0.5, 1, 2, 3, 4, and 5 hours after the last indinavir dose. Concentration-time data were analyzed using noncompartmental methods. Coadministration of Seville orange juice and indinavir resulted in a statistically significant increase in indinavir tmax (1.87 [1.65-2.22] vs. 1.25 [1.03-1.60] h; p < 0.05) without altering other pharmacokinetic parameter values. Grapefruit juice administration did not result in any changes in indinavir pharmacokinetics. Modulation of intestinal CYP3A4 by grapefruit juice and Seville orange juice did not alter the systemic availability of indinavir. The contribution of presystemic metabolism to indinavir interpatient variability appears to be small.
UR - http://www.scopus.com/inward/record.url?scp=0036784493&partnerID=8YFLogxK
U2 - 10.1177/009127002401382650
DO - 10.1177/009127002401382650
M3 - Article
C2 - 12362932
AN - SCOPUS:0036784493
SN - 0091-2700
VL - 42
SP - 1165
EP - 1170
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 10
ER -