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Population pharmacokinetics of intravenous acetaminophen and its metabolites in major surgical patients
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...
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Published in: | Journal of pharmacokinetics and pharmacodynamics 2014-06, Vol.41 (3), p.211-221 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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 (33–87), median weight (range) 74 kg (54–129). Patients received 1, 1.5 or 2 g of intravenous acetaminophen every 4–6 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 (V
C
) was 13.9 (4.41) L, peripheral (tissue) volume of distribution (V
T
) 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 (CL
PG
) was 8.92 (3.25) L/h, sulfation (CL
PS
) was 0.903 (3.47) L/h, and oxidation (CL
PO
) was 0.533 (7.90) L/h. The population mean (CV%) urinary clearances of parent acetaminophen (CL
RP
) was 0.137 (5.46) L/h, acetaminophen glucuronide (CL
RG
) was 3.81 (6.71) L/h, acetaminophen sulfate (CL
RS
) was 3.13 (4.32) L/h, and acetaminophen cysteine + mercapturate (CL
RO
) 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. |
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ISSN: | 1567-567X 1573-8744 |
DOI: | 10.1007/s10928-014-9358-0 |