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The Pharmacokinetic Profile of Intravenous Paracetamol in Adult Patients Undergoing Major Abdominal Surgery.
MedLine Citation:
PMID:  23149443     Owner:  NLM     Status:  Publisher    
BACKGROUND:: Intravenous (IV) paracetamol is commonly used in the postoperative period for the treatment of mild to moderate pain. The main pathways for paracetamol metabolism are glucuronidation, sulfation, and oxidation, accounting for approximately 55%, 30%, and 10% of urinary metabolites, respectively. The aim of this study was to describe the pharmacokinetics of IV paracetamol and its metabolites in adult patients after major abdominal surgery. METHODS:: Twenty patients were given 1 g of paracetamol by IV infusion at induction of anesthesia (Interval 1) and every 6 hours thereafter, with the final dose given at 48-72 hours (Interval 2). Plasma and urine samples were collected for up to 8 hours after infusion for both intervals. The samples were analyzed by high-performance liquid chromatography to determine the amount of paracetamol and its metabolites. The data were modeled in Phoenix WinNonlin using a user-defined ASCII parent-metabolite model with linear disposition, to obtain the estimates for volume of distribution, metabolic and urinary clearance. RESULTS:: Mean (95% confidence interval) metabolic clearance to paracetamol glucuronide increased from 0.06 (0.05-0.08) to 0.14 (0.11-0.18) L·h·kg, P value <0.001 and urinary clearance increased from 0.08 (0.07-0.09) to 0.14 (0.10-0.17) L·h·kg, P value 0.002. The mean (95% confidence interval) volume of distribution of paracetamol increased from 0.17 (0.12-0.21) to 0.43 (0.27-0.59) L·kg, P value 0.032. CONCLUSIONS:: After major abdominal surgery, there were apparent increases in the metabolic conversion to paracetamol glucuronide and its urinary clearance suggesting potential induction of paracetamol glucuronidation.
Katie H Owens; Natalie J Medlicott; Mathew Zacharias; Neil Curran; Sree Chary; Mark Thompson-Fawcett; David M Reith
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Publication Detail:
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  34     ISSN:  1536-3694     ISO Abbreviation:  Ther Drug Monit     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  -    
Other Details:
Languages:  ENG     Pagination:  713-721     Citation Subset:  -    
*School of Pharmacy, University of Otago †Anaesthesia and Intensive Care, Dunedin Hospital, Southern District Health Board ‡Dunedin Hospital, Southern District Health Board; §Surgical Sciences, Dunedin School of Medicine, University of Otago; and ¶Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
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