Paracetamol disposition and metabolite kinetics in patients with chronic renal failure

The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mea...

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Bibliographic Details
Published in:European journal of clinical pharmacology 1989-01, Vol.36 (3), p.291-297
Main Authors: PRESCOTT, L. F, SPEIRS, G. C, CRITCHLEY, J. A. J. H, TEMPLE, R. M, WINNEY, R. J
Format: Article
Language:English
Subjects:
Acetaminophen - analogs & derivatives
Acetaminophen - blood
Acetaminophen - pharmacokinetics
Acetaminophen - urine
Adult
Aged
Analgesics
Biological and medical sciences
Female
Half-Life
Humans
Kidney - metabolism
Kidney Failure, Chronic - metabolism
Male
Medical sciences
Middle Aged
Neuropharmacology
Pharmacology. Drug treatments
Time Factors
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Summary:The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mean plasma half-life of paracetamol from 2 to 8 h was similar in the 3 groups (2.1 to 2.3 h) but from 8 to 24 h it disappeared much more slowly in the renal failure patients (half-life 11.7 compared with 4.9 h in the healthy volunteers). Plasma concentrations of paracetamol glucuronide and sulphate conjugates were greatly increased in the patients with moderate renal failure and the mean plasma half-lives were 30.5 and 21.8 h respectively compared with about 3 h in the healthy volunteers. Plasma concentrations of these metabolites were even higher in the dialysis patients and there was no significant fall over 24 h. The cysteine and mercapturic acid conjugates of paracetamol could only be measured in plasma in the patients with renal failure and concentrations were very low. The fractional urinary recovery of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates was similar in healthy volunteers and patients with moderate renal failure.
ISSN:0031-6970
1432-1041
DOI:10.1007/BF00558162