Population pharmacokinetics of intravenous acetaminophen and its metabolites in major surgical patients

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• 作者：Katie H. Owens (1)
  Philip G. M. Murphy (2)
  Natalie J. Medlicott (1)
  Julia Kennedy (2)
  Mathew Zacharias (3)
  Neil Curran (3)
  Sree Sreebhavan (1)
  Mark Thompson-Fawcett (4)
  David M. Reith (4)
  
• 关键词：Acetaminophen ; Analgesia ; Surgery ; Population pharmacokinetics ; Drug metabolism ; Phoenix NLME
• 刊名：Journal of Pharmacokinetics and Pharmacodynamics
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：41
• 期：3
• 页码：211-221
• 全文大小：668 KB
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• 作者单位：Katie H. Owens (1)
  Philip G. M. Murphy (2)
  Natalie J. Medlicott (1)
  Julia Kennedy (2)
  Mathew Zacharias (3)
  Neil Curran (3)
  Sree Sreebhavan (1)
  Mark Thompson-Fawcett (4)
  David M. Reith (4)
  
  1. School of Pharmacy, University of Otago, P.O. Box 56, Dunedin, New Zealand
  2. University College Cork, Cork, Ireland
  3. Dunedin Hospital, Dunedin, New Zealand
  4. Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
  
• ISSN：1573-8744

文摘

Intravenous acetaminophen is a commonly used analgesic following surgery. The aims of this study were to determine the population pharmacokinetic profile of intravenous acetaminophen and its metabolites in adult surgical patients and to identify patient characteristics associated with acetaminophen metabolism in the postoperative period. 53 patients were included in the dataset; 28 were men, median age (range) 60?years?(33-7), median weight (range) 74?kg (54-29). Patients received 1, 1.5 or 2?g of intravenous acetaminophen every 4-?h. Plasma and urine samples were collected at various intervals for up to 6?days after surgery. Simultaneous modelling of parent acetaminophen and its metabolites was conducted in Phoenix? NLME?to estimate pharmacokinetic parameters. The population mean estimate (CV%) for central (plasma) volume of distribution of parent acetaminophen (VC) was 13.9 (4.41) L, peripheral (tissue) volume of distribution (VT) was?50.9?(2.96)?L, and intercompartmental clearance (Q) was?77.5?(9.29)?L/h. The population mean (CV%) metabolic clearances for glucuronidation (CLPG) was 8.92 (3.25)?L/h, sulfation (CLPS) was 0.903?(3.47)?L/h, and oxidation (CLPO) was 0.533?(7.90)?L/h. The population mean (CV%) urinary clearances of parent acetaminophen (CLRP) was 0.137?(5.46)?L/h, acetaminophen glucuronide (CLRG) was 3.81?(6.71)?L/h, acetaminophen sulfate (CLRS) was 3.13 (4.32)?L/h, and acetaminophen cysteine?+?mercapturate (CLRO) was 3.51 (9.98)?L/h. Age was found to be a significant covariate on the formation of acetaminophen glucuronide, and renal function (estimated as creatinine clearance) on the urinary excretion of acetaminophen glucuronide.