AEGiS-13IAC: Effect of food on the pharmacokinetics of nelfinavir (Viracept) administered twice daily.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Effect of food on the pharmacokinetics of nelfinavir (Viracept) administered twice daily.

Int Conf AIDS 2000 Jul 9-14; 13:44 (abstract no.. LbPeB7048)

Kurowski M, Kaeser B, Popescu M, Mroziekiewicz A, Arslan A, Staszewski S
HIV-LAB c/o Auguste-Viktoria Krankenhaus, Auguste Viktoria Krankenhaus, Berlin, Germany. Fax: +49-30-790 32 005, E-mail: labor-kurowski@t-online.de.

BACKGROUND: Nelfinavir (NFV) 1250mg BID has anti-retroviral efficacy comparable to the initially registered NFV 750mg TID regimen. In singledose studies in healthy volunteers, NFV exposure was increased under fed conditions compared to fasting.

OBJECTIVE: To investigate the effect of two different breakfasts on the pharmacokinetics (PK) of NFV at steady state during BID administration.

METHODS: Multiple dose, open-label, one-sequence crossover study in 21 healthy male volunteers. Study subjects received NFV 1250mg BID for 17 days. On day 14, NFV was administered with a standardized breakfast (BF) containing ca. 800 kcal (35 gr. fat), and on day 17 with a light BF of ca. 350 kcal (13 gr. fat). In addition, all other meals and fluid intake were standardized. Plasma samples were collected for 12h PK profiles. The food effect was evaluated with an ANOVA using log-transformed variables.

RESULTS: With the 800 kcal BF (reference), point estimates for NFV AUC(0-12h), Cmax, andC(1 -hour-post-dose) were 28.4 mg h/L, 3.64 mg/L, and 0.91 mg/L, respectively. After the 350 kcal BE, the estimate and ratio relative to reference in percent (95% CI) were: AUC(O-12h) 24.4 mg h/L or 86% (78% to93%), for Cmax 3.55 mg/L or 98% (9 1 % to 104%), and for C(1-h-post-dose) 0.88 mg/L or 97% (75% to 127%). Discussion: The reduced-calories BF had only a marginal and clinically not relevant effect on NFV exposure. After administration with a "light" BF, the AUC(O- 12h), Cmax, and C(1-h-post-dose) were reduced by 14%, 2%, and 3%, respectively, when compared to NFV dosed with a standard BE The wide 95% C1 forC(1-h-post-dose), a time when NFV plasma levels are usually lowest, are reflection of intra-individual variability. While intake with food is relevant for optimal NFV absorption (studies AG 1343-501 & JT-HS-82), our results are in line with data from these studies, indicating that the quantity of food and its fat content have only minimal effect on NFV absorption.

Keywords: AEGIS, Nelfinavir, Area Under Curve, Biological Availability, Food, Food-Drug Interactions, Fasting, Absorption, Male, pharmacokinetics, AIDS
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