title: The pharmacokinetics of the effervescent vs. conventional tramadol/paracetamol fixed-dose combination tablet in patients after total gastric resection.
abstract: BACKGROUND
  Tramadol/paracetamol is a fixed-dose combination prescribed for the relief of moderate to severe pain. The combination acts synergistically and guarantees the rapid onset of paracetamol and the prolonged analgesic effect of tramadol with good tolerability. These drugs are often used in various formulations in the treatment of patients with postoperative pain, e.g. after stomach resection. Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect the process of drug absorption. The aim of the research was an analysis of the pharmacokinetics of tramadol/paracetamol from effervescent and conventional tablets in patients after total gastrectomy.
  
  
  METHODS
  The research was carried out on patients after gastrectomy with Roux-en-Y reconstruction. The patients received two tramadol/paracetamol fixed-dose combination tablets in a single orally administered dose of 75/650 mg (2 × 37.5/325 mg). The patients were subjected to one of the two study drug group with: I. effervescent tablet (ET) (n = 14; mean [SD] age, 63.4 [10.1] years; weight, 75.5 [15.3]kg; and BMI, 26.0 [4.6]kg/m(2)) and II. conventional tablet (CT) (n = 12; mean [SD] age, 66.8 [7.7] years; weight, 79.8 [17.8]kg; and BMI, 27.4 [5.3]kg/m(2)). Blood samples were collected within 10 h after the drug administration. The plasma concentrations of tramadol and paracetamol were measured with validated HPLC (high-performance liquid chromatography) method with UV detection.
  
  
  RESULTS
  The comparison of the paracetamol and tramadol C(max) ratio for the ET group with that of the CT group gave ratios of 1.16 [90% confidence interval (CI) 1.06, 1.27] and 0.86 (90% CI 0.72, 1.02), respectively. The comparison of the paracetamol and tramadol AUC(0-t) ratio for the ET group with that of the CT group showed ratios of 0.99 (90% CI 0.88, 1.10) and 1.00 (90% CI 0.82, 1.22), respectively. The comparison of the difference for the effervescent and conventional formulation gave an estimated decrease in t(max) of 0.5 h for paracetamol and 0.13 h for tramadol.
  
  
  CONCLUSIONS
  In view of the changes in the pharmacokinetics of paracetamol and tramadol in the patients after gastric resection for both formulations compared the conventional tablet seems to be more appropriate due to the comparable rate of absorption of both substances, higher concentrations of tramadol and comparable exposure to paracetamol.
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences Poznań, Poland. Electronic address: szalekedyta@wp.pl.
authors.forename: Edyta
authors.initials: E
authors.lastname: Szałek
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Karbownik
authors.affiliation: 1st Department of Surgical Oncology and General Surgery Department, Wielkopolska Cancer Centre, Poznań, Poland.
authors.forename: Dawid
authors.initials: D
authors.lastname: Murawa
authors.affiliation: 1st Department of Surgical Oncology and General Surgery Department, Wielkopolska Cancer Centre, Poznań, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Połom
authors.affiliation: Department of Inorganic and Analytical Chemistry, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Urbaniak
authors.affiliation: Polpharma Biologics, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
authors.affiliation: Department of Animal Science, Iowa State University, IA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Wolc
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences Poznań, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Więckiewicz
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences Poznań, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
authors.affiliation: Department of Inorganic and Analytical Chemistry, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Zenon J
authors.initials: ZJ
authors.lastname: Kokot
authors.affiliation: 1st Department of Surgical Oncology and General Surgery Department, Wielkopolska Cancer Centre, Poznań, Poland; Cancer Pathology Department, Clinic of Oncology, University of Medical Sciences, Poznań, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Murawa
authors.affiliation: Division of Cardiology-Intensive Care, University of Medical Sciences, Poznań, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Burchardt
authors.affiliation: Department of General Surgery, Leszno Regional Hospital, Leszno, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Cieśla
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000368:Aged; D000700:Analgesics / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004338:Drug Combinations; D005260:Female; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D014147:Tramadol / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000700:Analgesics; D004338:Drug Combinations; D013607:Tablets; D000082:Acetaminophen; D014147:Tramadol
keywords: Absorption; Effervescent; Gastrectomy; Paracetamol; Tablet; Tramadol