Pharmacokinetic variations of acetaminophen according to liver dysfunction and portal hypertension status
Summary Aim : 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), bein...
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Published in | Alimentary pharmacology & therapeutics Vol. 20; no. 1; pp. 29 - 36 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.07.2004
Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | Summary
Aim : 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0269-2813 1365-2036 |
DOI: | 10.1111/j.1365-2036.2004.02022.x |