title: Pharmacokinetics of paracetamol in patients with chronic pancreatitis.
abstract: BACKGROUND
  Chronic pancreatitis (CP) is a progressive, irreversible disease causing damage of the gland. Abdominal pains are a typical symptom of pancreatitis both in the chronic and acute form. Paracetamol is one of analgesics used for treating mild or moderate pain. Functional and anatomical changes in the gastrointestinal tract caused by pancreatitis may influence on the pharmacokinetics of administered drugs.
  
  
  METHODS
  In the present study we analysed the pharmacokinetics of paracetamol after oral and intravenous administration to patients with CP. The patients were allocated to one of the two groups of the drug under study: I iv, intravenous administration of paracetamol 1000mg (n=17; mean [SD] age, 46.18 [13.78] years; and BMI, 22.03 [2.62]kg/m(2)) and II po, oral administration of paracetamol 1000mg (n=17; mean [SD] age, 48.29 [10.08] years; and BMI, 22.50 [2.92]kg/m(2). The plasma concentrations of paracetamol and its metabolite (glucuronide) were measured with the validated high-pressure liquid chromatography (HPLC) method with ultraviolet (UV) detection.
  
  
  RESULTS
  The main pharmacokinetic parameters for paracetamol after iv and po administration to patients with CP were as follows: Cmax, 19.00 [4.50] and Cmax, 9.26 [3.35]μg/ml; AUC0-t, 42.37 [13.92] and 36.68 [11.7]μg×h/mL, respectively. After iv and po administration the AUC ratio between the metabolite (glucuronide) and paracetamol was enhanced.
  
  
  CONCLUSIONS
  The research findings revealed that patients with chronic pancreatitis had lower concentrations of paracetamol. Therefore, it may be necessary to apply additional analgesic therapy. Moreover, we observed enhanced glucuronidation in our patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Medical University of Gdańsk, Gdańsk, Poland. Electronic address: mag.siepsiak@gmail.com.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Siepsiak
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Medical University of Poznań, Poznań, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Szałek
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Medical University of Poznań, Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Karbownik
authors.affiliation: Polpharma Biologics, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
authors.affiliation: Department of Public Nursing and Health Promotion, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Marzanna
authors.initials: M
authors.lastname: Mziray
authors.affiliation: Department of Gastroenterology and Hepatology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Krystian
authors.initials: K
authors.lastname: Adrych
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Medical University of Poznań, Poznań, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics*; D061605:Administration, Intravenous; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics; D005260:Female; D020719:Glucuronides / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D050500:Pancreatitis, Chronic / Q000097:blood / Q000378:metabolism*
chemical_list: D018712:Analgesics, Non-Narcotic; D020719:Glucuronides; D000082:Acetaminophen
keywords: Chronic pancreatitis; Metabolite; Paracetamol; Pharmacokinetics