The serotonin-norepinephrine reuptake inhibitor desvenlafaxine has linear and dose-proportional pharmacokinetics from 25 to 900 mg. The effect of diet on the pharmacokinetics, safety, and tolerability of desvenlafaxine in healthy volunteers (N=33) was assessed in this single-dose, open-label, randomized, 4-period, 4-sequence, crossover, inpatient study. Desvenlafaxine 200 mg was administered after an overnight fast or after a low-, medium-, or high-fat breakfast. Blood samples were obtained over 72 hours. Pharmacokinetic parameters were compared across dosing conditions using analysis of variance. The median time to peak concentration for desvenlafaxine was approximately 6 hours under fasting conditions and was delayed by approximately 2 to 4 hours when administered with food. Diet did not affect apparent oral-dose clearance and apparent terminal-phase elimination half-life values. Except for peak plasma concentration under high-fat conditions, both peak plasma concentration and area under the plasma concentration-versus-time curve met bioequivalence test criteria under each dietary condition, compared with an overnight fast (90% confidence interval within 80%-125% limits). The minor increase in peak plasma concentration under high-fat conditions was not clinically relevant. Desvenlafaxine was well tolerated under fasting and fed conditions. These results suggest that pharmacokinetics should not be a factor when considering whether to administer desvenlafaxine with or without food.
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