A Phase 1, Randomized, Single‐Dose Crossover Pharmacokinetic Study to Investigate the Effect of Food Intake on Absorption of Orteronel (TAK‐700) in Healthy Male Subjects

Abstract

This study aimed to determine the impact of food on the pharmacokinetics of orteronel, an investigational nonsteroidal, reversible selective inhibitor of 17,20-lyase. In this open-label, randomized crossover study, healthy subjects received single doses of orteronel 400 mg with a low-fat meal, a high-fat meal, and under fasting conditions in a randomized sequence. Plasma concentrations of orteronel and its primary M-I metabolite were determined by ultra-performance liquid chromatography, and pharmacokinetic parameters were evaluated using mixed-effects analysis of variance model. Compared with fasting conditions, the oral bioavailability of orteronel was increased under fed conditions. The least-squares mean ratio for area under the plasma concentration-time curve after a low-fat breakfast was 135% (90% confidence interval [CI], 126%-145%) compared with fasting conditions. Similarly, after a high-fat breakfast, the corresponding value was 142% (90%CI, 132%-152%). No unexpected safety concerns were raised with orteronel 400 mg administered in the fasted state or after either a high-fat or a low-fat meal; mild adverse events were experienced by 36% of the healthy male subjects.

Evaluation of real-life dosing of oral medicines with respect to fluid and food intake in a Dutch-speaking population

“…Besides beverages, the intake of food is recommended for certain drug substances to increase their oral bioavailability, especially for lipophilic compounds . However, as stated by Singh, there is still no rational scientific basis to predict the effect of food for a particular chemical entity or a chemical class of therapeutic agents .…”

“…Co-administration of alcohol has been shown to be responsible Besides beverages, the intake of food is recommended for certain drug substances to increase their oral bioavailability, especially for lipophilic compounds. 7,26 However, as stated by Singh, there is still no rational scientific basis to predict the effect of food for a particular chemical entity or a chemical class of therapeutic agents. 27,28 Moreover, the standardized high-fat meal of approximately 800-1000 calories used in clinical trials does not always reflect the meal con- with NSAIDs.…”