title: An assessment of the pharmacokinetics of a sustained-release formulation of a tramadol/acetaminophen combination in healthy subjects.
abstract: OBJECTIVE
  To provide consistent pain relief and improve convenient sustained release (SR), a fixed-dose combination tramadol/acetaminophen tablet was formulated. This study aimed to evaluate the pharmacokinetic profiles of an SR 75-mg tramadol/650-mg acetaminophen formulation after a single dose compared with an immediate release (IR) 37.5-mg tramadol/325-mg acetaminophen formulation after 2 doses and at steady state and to assess the effect of food on the pharmacokinetic SR formulation profile after a single dose.
  
  
  METHODS
  Two clinical trials were conducted: (1) an open-label, randomized, 3-period, 3-treatment, crossover study to assess the pharmacokinetic SR (one 75-mg tramadol/650-mg acetaminophen combination tablet) formulation profiles after a single dose and IR (one 37.5-mg tramadol/325-mg acetaminophen combination tablet q6h for 2 doses) formulation profiles after 2 doses and the effect of food intake on healthy male subjects and (2) an open, randomized, 2-period, 2-treatment multiple dose crossover study to evaluate the steady-state pharmacokinetic SR and IR formulation profiles. Safety assessments were performed.
  
  
  RESULTS
  Forty-three subjects completed each study protocol. The SR combination tramadol/acetaminophen formulation was clinically and statistically equivalent to the IR combination formulation in the fasting state. When tramadol and acetaminophen tablets were administered with food, the time to peak plasma concentrations and the tramadol/acetaminophen absorption were unaffected. There was no serious adverse event reported.
  
  
  CONCLUSIONS
  The SR combination tramadol/acetaminophen tablet exhibited similar exposure and absorption rates compared with those of the IR formulation of tramadol, O-desmethyltramadol, and acetaminophen. The SR formulation may be more convenient for patients and has the potential to enhance compliance and pain control. ClinicalTrials.gov identifier: NCT01880125.
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Im
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Jeon
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Yunjeong
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Yungjin Pharmaceutical Co, Ltd, Gangdong-gu, Seoul, Republic of Korea.
authors.forename: Dong-Joon
authors.initials: DJ
authors.lastname: Oh
authors.affiliation: Department of Pharmacology, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Ji-Seok
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: Yungjin Pharmaceutical Co, Ltd, Gangdong-gu, Seoul, Republic of Korea.
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Shin
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; Department of Pharmacology, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Soo-Wan
authors.initials: SW
authors.lastname: Chae
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. Electronic address: mgkim@jbnu.ac.kr.
authors.forename: Min-Gul
authors.initials: MG
authors.lastname: Kim
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004338:Drug Combinations; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D014147:Tramadol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D013607:Tablets; C080580:O-demethyltramadol; D000082:Acetaminophen; D014147:Tramadol
keywords: acetaminophen; food effect; pharmacokinetics; sustained release; tramadol