Pharmacokinetics of Nelfinavir (Viracept 250 mg tablet):  Effect of Food Intake on Single Dose PK Parameters

 

C. Petersen¹*, E. Pun¹, E. Randinitis², C. Bramson², R. Strada¹, E. Daniels¹

 

¹Agouron Pharmaceuticals Inc., A Pfizer Company, San Diego, CA and ²Pfizer Global Research and Development, Ann Arbor, MI.

 

Background: Highly active antiretroviral therapy has led to markedly improved survival and decreased disease related morbidity in HIV⁺ individuals. Current efforts to improve therapy include optimizing the use of established agents, identifying new agents and new classes of drugs and decreasing the side effects of therapy. The need for food intake with Viracept has been established, but the effect of varying food intake on optimizing pharmacokinetics has not been well studied.

Methods: A phase I, randomized, open-label crossover study to evaluate the impact of total kilocalories and fat content on single-dose pharmacokinetic parameters of the nelfinavir 250 mg tablet formulation in 24 normal healthy volunteers was performed. Subjects were dosed with 1,250 mg of nelfinavir 4 times at one-wk intervals and 12-hr PK profiles were collected following each of the doses. Each subject was assigned 4 food intakes prior to dosing (fasting, 125 kcal with 20% fat, 500 kcal with 20% fat, and 1000 kcal with 50% fat) using a Latin square design.

Results:

 

 

 

Conclusions: This exploratory PK study indicates 1) food intake has a marked effect on nelfinavir PK with highest levels achieved after the greatest food intake. AUC values that increased 3–5 fold of those achieved in the fasting state were achieved with meals containing 500-1000 kcal and 20%–50% fat; 2) M8 concentrations rose with increasing food intake, but the percentage of M8 relative to nelfinavir remained the same, approximately 15%-20%; and 3) the contribution of different quantities of fat intake on PK and the effect of food on steady state PK in HIV patients require further study.