Single-dose pharmacokinetics of paracetamol and its conjugates in Chinese non-insulin-dependent diabetic patients with renal impairment.
OBJECTIVE
A single oral dose of paracetamol (20 mg.kg-1) was given to 38 Chinese patients with non-insulin-dependent diabetes mellitus (NIDDM) who had either normal renal function or varying degrees of renal impairment, with creatinine clearances ranging from 4 to 123 ml.min-1.1.73 m-2. The plasma and urinary concentrations of paracetamol and its major metabolites were measured by high-performance liquid chromatography (HPLC).


RESULTS
The absorption and elimination of paracetamol were unaffected by renal impairment. However, the area under the plasma concentration time curve and the elimination half-life of paracetamol metabolites increased significantly with worsening renal insufficiency. Mean renal clearances of paracetamol and its conjugates were significantly reduced in these subjects. There was no evidence of altered metabolic activation with renal impairment.


CONCLUSIONS
The results demonstrate that paracetamol disposition is minimally affected by diabetic nephropathy; however, extensive accumulation of conjugates may occur.
Chan
M T
MT
Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.
Anderson
P J
PJ
Chan
J C
JC
Lau
G S
GS
Critchley
J A
JA
D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006207:Half-Life; D006723:Hong Kong / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged
D000082:Acetaminophen