Title: Postmenstrual age and CYP2D6 polymorphism determine tramadol O-demethylation in critically ill neonates and infants
Authors: Allegaert, Karel ×
Van Schaik, Ron H. N
Vermeersch, Steve
Verbesselt, René
Cossey, Veerle
Vanhole, Christine
Van Fessem, Marianne
de Hoon, Jan
Van den Anker, John N #
Issue Date: Jun-2008
Publisher: Int pediatric research foundation, inc
Series Title: Pediatric research vol:63 issue:6 pages:674-679
Abstract: To document determinants of O-demethylation in critically ill (pre)term neonates and infants, tramadol (M) and O-demethyl tramadol (M1) concentrations were quantified in eighty-six 24 h urine collections and 168 plasma samples. A significant correlation of urine log M/M1 (0.98, SD 0.66) and plasma log M/M1 (0.78, SD 0.45) with postmenstrual age (PMA) (r = -0.69 and -0.65) was observed. One-way analysis of variance documented a significant decrease in urine log and plasma log M/M1 with increasing CYP2D6 activity score (F value 11.6 and 22.55). PMA and CYP2D6 activity score determined the urine and plasma log M/M1 (R-2 0.59 and 0.64) in a forward multiple regression model. We therefore conclude that PMA and CYP2D6 polymorphisms determined O-demethylation activity in (pre)term neonates and young infants, illustrating the impact of pharmacogenetics on drug metabolism in neonates although a relevant part of the interindividual varaibility remained unexplained. Besides compound-specific relevance, CYP2D6 iso-enzyme specific data on in vivo ontogeny of O-demethylation can contribute to safer and more effective administration of drugs metabolized by the same route in this population.
ISSN: 0031-3998
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Section Newborn (-)
Clinical Pharmacology Centre (-)
× corresponding author
# (joint) last author

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