Effect of a High-Fat Meal on the Pharmacokinetics of the HIV Integrase Inhibitor Cabotegravir

Parul Patel, Susan L Ford, Yu Lou, Kalpana Bakshi, Allan R Tenorio, Zhiping Zhang, Rennan Pan, William Spreen, Parul Patel, Susan L Ford, Yu Lou, Kalpana Bakshi, Allan R Tenorio, Zhiping Zhang, Rennan Pan, William Spreen

Abstract

Cabotegravir is an integrase inhibitor in clinical development for the treatment and prevention of HIV infection using oral tablets for short-term, lead-in use before subsequent administration of a long-acting injectable formulation. This phase 1, single-center, randomized, 2 × 2 crossover study evaluated the effect of a high-fat meal on the pharmacokinetics (PK) of oral cabotegravir. Healthy adults received oral cabotegravir 30 mg as a single dose on 2 separate occasions, either after fasting or following a high-fat meal (∼53% fat, ∼870 kcal). Safety evaluations and serial PK samples were collected, and a mixed-effects model was used to determine within-participant treatment comparison of noncompartmental PK parameters. Twenty-four patients were enrolled and had a mean body mass index of 25.6 kg/m2 ; 67% were male. Compared with the fasting state, coadministration of cabotegravir with a high-fat meal increased plasma cabotegravir area under the concentration-time curve and maximal drug concentration, each by 14%. The slight 14% to 17% increase in exposure associated with a high-fat, high-calorie meal was not considered clinically significant. No grade 3/4 adverse events (AEs), drug-related AEs, or AEs leading to discontinuation were reported.

Trial registration: ClinicalTrials.gov NCT02799264.

Keywords: absorption; food; high-fat; integrase inhibitor; pharmacokinetics.

© 2018, The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Figures

Figure 1
Figure 1
Mean (SD) concentration‐time profiles of cabotegravir after administration in a fasted state or with a high‐fat meal.

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Source: PubMed

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