Effect of food on the pharmacokinetics of (-) and (+) dOTC when administered as an oral racemate.

ABSTRACT

The objective of this study was to evaluate the effect of food on the pharmacokinetics of racemic dOTC, a nucleoside analogue reverse transcriptase inhibitor, in adult male volunteers. Twelve healthy adult male subjects were enrolled in a randomized, open-label, single-dose crossover study. All were nonsmoking, within 15% of ideal body weight, and between 18 and 50 years of age. Subjects received single oral doses of 800mg racemic dOTC, in random order, either fed or fasted. The meal given to fed subjects was the standard Food and Drug Administration high-fat breakfast, and all subjects completed both study periods. Sixteen plasma samples for pharmacokinetic assessments were collected for 72 hours following dosing and assayed for (-) and (+) dOTC concentrations. Area under the plasma concentration-time curve (AUC), maximum observed plasma concentration (Cmax), and time to maximum concentration (tm) were determined for each enantiomer by standard noncompartmental techniques. Statistical hypothesis testing was by Wilcoxon signed rank, and the two one-sided tests procedure was used to determine bioequivalence between thefed and fasted study periods. The only effect of coadministration of racemic dOTC with food was a delay in time to peak concentration (t(max) of between 0.6 and 0.7 hours for both (-) and (+) dOTC stereoisomers (p < or =0.02). Neither AUC (p > or = 0.10) nor Cmax (p > or = 0.35) differed significantly between the fed and fasted study periods for either (-) or (+) dOTC. Both AUC and Cmax were equivalent between the fed and fasted study periods. It was concluded that there is no clinically significant effect of a high-fat meal on the pharmacokinetics of either (-) or (+) dOTC when administered orally as a racemic mixture.