PEDIATRICS Vol. 55 No. 6 June 1975, pp. 818-825
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Pharmacokinetics of Acetaminophen in the Human Neonate: Formation of Acetaminophen Glucuronide and Sulfate in Relation to Plasma Bilirubin Concentration and D-Glucaric Acid Excretion

Gerhard Levy Pharm.D.1, Narinder N. Khanna M.B.1, David M. Soda M.S.1, Osami Tsuzuki Ph.D.1, and Leo Stern M.D.1

1 Department of Pharmaceutics, State University of New York, Buffalo, the Department of Pediatrics, Catherine Booth Hospital, Montreal, and the McGill University-Montreal Children's Hospital Research Institute, Montreal

The purpose of this study was to determine if certain physiologic parameters (plasma bilirubin concentration and urinary excretion rate of D-glucaric acid) can be used to predict a newborn infant's ability to eliminate a phenolic drug. and particularly to predict the ability to conjugate that drug with glucuronic acid. Twelve healthy 2-to 3-day-old full-term infants with plasma bilirubin concentrations of 1.0 to 11.6 mg/100 ml and D-glucaric acid excretion rates of 0.131 to 0.345 mg/kg/day received a single oral dose of acetaminophen, 12 mg/kg. Urine was collected serially for 48 hours and analyzed for acetaminophen, acetaminophen glucuronide, acetaminophen sulfate, and D-glucaric acid. The biologic half-life of acetaminophen was 3.5 ± 0.85 hours (average ± SD) as compared to average values of 1.9 to 2.2 hours observed in five reported studies on a total of 39 adults. The rate constant for acetaminophen glucuronide formation in neonates was considerably smaller, on the average, than in adults but the average rate constant for acetaminophen sulfate formation was somewhat larger than in adults. There is no statistically significant correlation between these rate constants and either plasma bilirubin concentration or D-glucaric acid excretion. The results of this study suggest that the limited ability of neonates to conjugate phenolic drugs with glucuronic acid is compensated to a degree by a well-developed capability for sulfate conjugation.

Submitted on July 31, 1974
Accepted on October 18, 1974




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