The effect of different meal types on the pharmacokinetics of darunavir (TMC114)/ritonavir in HIV-negative healthy volunteers.
This open-label, randomized, crossover study investigated the bioavailability, short-term safety, and tolerability of darunavir (TMC114) coadministered with low-dose ritonavir under fasted conditions and after different meal types in HIV-negative healthy volunteers. All volunteers received ritonavir 100 mg twice daily on days 1 to 5, with a single darunavir 400-mg tablet given on day 3 (darunavir/rtv). Pharmacokinetic parameters for darunavir and ritonavir were determined under fasted conditions and following a standard breakfast, a high-fat breakfast, a nutritional protein-rich drink, or a croissant with coffee. Administration of darunavir/rtv in a fasting state resulted in a decrease in darunavir C(max) and AUC(last) of approximately 30% compared with administration after a standard meal. No significant differences in darunavir plasma concentrations were observed between different fed states. Darunavir/rtv should therefore be administered with food, but exposure to darunavir is not affected by the type of meal.
Sekar
Vanitha
V
Tibotec, Inc, Yardley, Pennsylvania, USA.
Kestens
Dries
D
Spinosa-Guzman
Sabrina
S
De Pauw
Martine
M
De Paepe
Els
E
Vangeneugden
Tony
T
Lefebvre
Eric
E
Hoetelmans
Richard M W
RM
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D000069454:Darunavir; D004338:Drug Combinations; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018023:HIV Seronegativity; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir