title: Pharmacokinetic variations of acetaminophen according to liver dysfunction and portal hypertension status.
abstract: OBJECTIVE
  To study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis.
  
  
  METHODS
  Oral acetaminophen (1000 mg) was administered to seven healthy subjects and 14 patients with cirrhosis (nine Child-Pugh A or B and five Child-Pugh C grade), being five without and nine with oesophageal varices. Plasma levels of acetaminophen and its metabolites were determined by HPLC.
  
  
  RESULTS
  Patients showed a higher mean area under the curve concentration-time (67.4 +/- 22.4 mg h/L vs. 38.8 +/- 4.3 mg h/L; P = 0.01), a lower clearance (166.7 +/- 85.0 mL/min vs. 367.8 +/- 62.5 mL/min; P = 0.01) and higher elimination half-life (3.8 +/- 1.1 h vs. 2.0 +/- 0.4 h; P = 0.01) of acetaminophen than healthy volunteers. The appearance in blood and the urinary excretion of metabolites in patients did not differ from healthy subjects. Absorption profile was faster in patients. Patients with lower mean and systolic arterial pressure had lower AUC of acetaminophen, independently of liver dysfunction stage.
  
  
  CONCLUSIONS
  Patients with cirrhosis had a higher AUC and lower clearance of acetaminophen. Acetaminophen attained earlier therapeutic concentrations in patients with oesophageal varices. Mean and systolic arterial pressures were significantly associated with AUC suggesting the importance of the haemodynamic function on the pharmacokinetics of acetaminophen in patients with cirrhosis.
authors.affiliation: Unidad de Farmacología Clínica, Hospital General Universitario, y Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Miguel Hernández, San Juan de Alicante, Spain. zapater_ped@gva.es
authors.forename: P
authors.initials: P
authors.lastname: Zapater
authors.forename: M C
authors.initials: MC
authors.lastname: Lasso de la Vega
authors.forename: J F
authors.initials: JF
authors.lastname: Horga
authors.forename: J
authors.initials: J
authors.lastname: Such
authors.forename: R
authors.initials: R
authors.lastname: Frances
authors.forename: A
authors.initials: A
authors.lastname: Esteban
authors.forename: J M
authors.initials: JM
authors.lastname: Palazòn
authors.forename: F
authors.initials: F
authors.lastname: Carnicer
authors.forename: S
authors.initials: S
authors.lastname: Pascual
authors.forename: M
authors.initials: M
authors.lastname: Pérez-Mateo
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004932:Esophageal and Gastric Varices / Q000150:complications / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen