title: Pharmacokinetic evaluation of tapentadol extended-release tablets in healthy subjects.
abstract: OBJECTIVE
  To evaluate serum pharmacokinetics of tapentadol administered to healthy subjects as extended-release (ER) tablets.
  
  
  METHODS
  Seven 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.
  
  
  METHODS
  Clinical research settings in the United States and The Netherlands.
  
  
  METHODS
  Healthy males and females were enrolled into seven studies; one study enrolled only Japanese males.
  
  
  METHODS
  In 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.
  
  
  METHODS
  Maximum 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Janssen Research & Development, LLC, New Jersey.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Zannikos
authors.affiliation: Janssen Research & Development, LLC, Beerse, Belgium.
authors.forename: Johan W
authors.initials: JW
authors.lastname: Smit
authors.affiliation: Grünenthal GmbH, Aachen, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Stahlberg
authors.affiliation: Grünenthal GmbH, Aachen, Germany.
authors.forename: Birger
authors.initials: B
authors.lastname: Wenge
authors.affiliation: Janssen Research & Development, LLC, Beerse, Belgium.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Hillewaert
authors.affiliation: Janssen Research & Development, LLC, New Jersey.
authors.forename: Mila S
authors.initials: MS
authors.lastname: Etropolski
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004435:Eating; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009426:Netherlands; D010636:Phenols / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013607:Tablets; D000077432:Tapentadol; D013810:Therapeutic Equivalency; D014481:United States; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D010636:Phenols; D013607:Tablets; D000077432:Tapentadol