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 (R2 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.
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Abbreviations
- M:
-
tramadol
- M1:
-
O-demethyl tramadol
- M2:
-
N-demethyl tramadol
- PMA:
-
postmenstrual age, weeks
- PNA:
-
postnatal age, days
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Supported by the Clinical Research Fund of the University Hospitals Leuven, Belgium (to K.A.), and by grant HD45993 (NICHD) and RR19729 (NCRR) (to J.N.v.d.A.).
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Allegaert, K., van Schaik, R., Vermeersch, S. et al. Postmenstrual Age and CYP2D6 Polymorphisms Determine Tramadol O-demethylation in Critically Ill Neonates and Infants. Pediatr Res 63, 674–679 (2008). https://doi.org/10.1203/PDR.0b013e31816ff712
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DOI: https://doi.org/10.1203/PDR.0b013e31816ff712
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