• Peter N Zannikos, Johan W Smit, Hans-Jürgen Stahlberg, Birger Wenge, Vera M Hillewaert, and Mila S Etropolski.
• Janssen Research & Development, LLC, New Jersey.
• J Opioid Manag. 2013 Jul 1;9(4):291-300.

ObjectiveTo evaluate serum pharmacokinetics of tapentadol administered to healthy subjects as extended-release (ER) tablets.DesignSeven single-dose studies (five randomized, crossover, bioequivalence studies; a study in Japanese men; and a randomized, crossover, effects-of-food study) and one repeated-dose study.SettingClinical research settings in the United States and The Netherlands.Patients Or ParticipantsHealthy males and females were enrolled into seven studies; one study enrolled only Japanese males.InterventionsIn the bioequivalence studies, subjects first received one polyethylene oxide- or hypromellose-based tapentadol ER tablet (50, 100, 150, 200, or 250 mg; one dose per study), then (after washout) the other formulation (matching dose). In all other studies, subjects received polyethylene oxide-based tapentadol ER tablets. In the repeated-dose study, subjects received one 250 mg tablet, then (after washout) one 250 mg tablet every 12 hours (five doses). In the food-effect study, subjects received one 250 mg tablet within 30 minutes after a high-fat meal or after 10 hours of fasting. In the study in Japanese men, subjects received one 100 mg tablet.Main Outcome MeasuresMaximum tapentadol concentrations (Cmax) were typically observed 5 hours after dosing. Mean terminal half-life values ranged from 4.4 to 5.9 hours. Tapentadol Cmax and AUC values increased proportionally following single ER (polyethylene oxide-based tablets) doses of 50 to 250 mg. Trough tapentadol concentrations increased during repeat dosing until reaching steady-state by the third dose. Serum Cmax and area under the concentration-time curve (AUC) values at steady state were 1.6 and 1.9 times higher relative to single-dose administration. Coadministration of the 250 mg dose with a high-fat meal increased Cmax and AUC values by an average of < 17 percent.ConclusionsThe pharmacokinetics of tapentadol ER are consistent after repeated and single-dose administration. Tapentadol ER may be administered without regard to food intake. No clinically significant differences were observed in the pharmacokinetics of tapentadol between Japanese and Caucasian subjects.

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