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 |
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Oxford, UK
Blackwell Science Ltd
01.07.2004
Blackwell |
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Abstract | 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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AbstractList | 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. AIMTo study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis.METHODSOral 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.RESULTSPatients 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.CONCLUSIONSPatients 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. To study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis. 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. 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. 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. 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. |
Author | Frances, R. Pérez‐Mateo, M. Such, J. Esteban, A. Carnicer, F. Lasso de la Vega, M. C. Palazòn, J. M. Pascual, S. Zapater, P. Horga, J. F. |
Author_xml | – sequence: 1 givenname: P. surname: Zapater fullname: Zapater, P. – sequence: 2 givenname: M. C. surname: Lasso de la Vega fullname: Lasso de la Vega, M. C. – sequence: 3 givenname: J. F. surname: Horga fullname: Horga, J. F. – sequence: 4 givenname: J. surname: Such fullname: Such, J. – sequence: 5 givenname: R. surname: Frances fullname: Frances, R. – sequence: 6 givenname: A. surname: Esteban fullname: Esteban, A. – sequence: 7 givenname: J. M. surname: Palazòn fullname: Palazòn, J. M. – sequence: 8 givenname: F. surname: Carnicer fullname: Carnicer, F. – sequence: 9 givenname: S. surname: Pascual fullname: Pascual, S. – sequence: 10 givenname: M. surname: Pérez‐Mateo fullname: Pérez‐Mateo, M. |
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Cites_doi | 10.1007/s002280050071 10.1002/hep.1840220114 10.1016/0016-5085(88)90441-6 10.2165/00002018-199717010-00004 10.1093/bja/87.4.638 10.1124/dmd.31.12.1499 10.1136/bmj.1.6073.1384 10.1016/S0016-5085(76)80320-4 10.1055/s-2003-42641 10.1007/BF00561743 10.1038/clpt.1983.14 10.1016/0378-4347(92)80483-7 10.2165/00003088-198611030-00006 10.1056/NEJM197511132932017 |
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Keywords | Vascular disease Paracetamol Analgesic Portal circulation disease Digestive system Antimigrainous agent Liver Portal hypertension Antipyretic Cardiovascular disease Digestive diseases Pharmacokinetics |
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fullname: Laffi G – volume: 33 start-page: 550 year: 1995 ident: e_1_2_10_18_2 article-title: Pharmacokinetic‐pharmacodynamic and metabolite modelling with TopFit publication-title: Int J Clin Pharmacol Ther contributor: fullname: Tanswell P – ident: e_1_2_10_4_2 doi: 10.2165/00002018-199717010-00004 – ident: e_1_2_10_19_2 doi: 10.1093/bja/87.4.638 – ident: e_1_2_10_3_2 doi: 10.1124/dmd.31.12.1499 – ident: e_1_2_10_6_2 doi: 10.1136/bmj.1.6073.1384 – volume: 70 start-page: 1108 year: 1976 ident: e_1_2_10_14_2 article-title: Splanchnic hemodynamics in cirrhotic patients with esophageal varices and gastrointestinal bleeding publication-title: Gastroenterology doi: 10.1016/S0016-5085(76)80320-4 contributor: fullname: Lebrec D – ident: e_1_2_10_2_2 doi: 10.1055/s-2003-42641 – volume: 624 start-page: 99 year: 1979 ident: e_1_2_10_10_2 article-title: Paracetamol (acetaminophen) clearance in patients with cirrhosis of the liver publication-title: Acta Med Scand Suppl contributor: fullname: Andreasen PB – volume: 25 start-page: 283 year: 1978 ident: e_1_2_10_8_2 article-title: Elimination of paracetamol in chronic liver disease publication-title: Acta Hepatogastroenterol (Stuttg) contributor: fullname: Arnman R – volume: 34 start-page: 299 year: 1996 ident: e_1_2_10_16_2 article-title: Acetaminophen plasma level after oral administration in liver cirrhotic patients suffering from schistosomal infection publication-title: Int J Clin Pharmacol Ther contributor: fullname: El‐Azab G – ident: e_1_2_10_7_2 doi: 10.1007/BF00561743 – ident: e_1_2_10_9_2 doi: 10.1038/clpt.1983.14 – ident: e_1_2_10_17_2 doi: 10.1016/0378-4347(92)80483-7 – ident: e_1_2_10_12_2 doi: 10.2165/00003088-198611030-00006 – volume: 7 start-page: 898 year: 1983 ident: e_1_2_10_11_2 article-title: Pharmacokinetics and metabolism of acetaminophen in normal, alcoholic and cirrhotic subjects publication-title: Gastroenterol Clin Biol contributor: fullname: Villeneuve JP – ident: e_1_2_10_15_2 doi: 10.1056/NEJM197511132932017 |
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Aim : To study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis.
Methods : Oral acetaminophen... To study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis. Oral acetaminophen (1000 mg) was... Summary Aim : To study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis. Methods : Oral acetaminophen... AIMTo study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis.METHODSOral acetaminophen (1000 mg) was... |
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SubjectTerms | Acetaminophen - administration & dosage Acetaminophen - pharmacokinetics Administration, Oral Analgesics, Non-Narcotic - administration & dosage Analgesics, Non-Narcotic - pharmacokinetics Area Under Curve Biological and medical sciences Chromatography, High Pressure Liquid Digestive system Esophageal and Gastric Varices - complications Esophageal and Gastric Varices - metabolism Female Gastroenterology. Liver. Pancreas. Abdomen Half-Life Humans Liver Cirrhosis - complications Liver Cirrhosis - metabolism Male Medical sciences Middle Aged Pharmacology. Drug treatments Prospective Studies |
Title | Pharmacokinetic variations of acetaminophen according to liver dysfunction and portal hypertension status |
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