Developmental pharmacology of tramadol during infancy: ontogeny, pharmacogenetics and elimination clearance

Abstract

The phenotypic observations might in part explain unanticipated (side-)effects of tramadol. In addition to the compound-specific clinical implications, it is important to stress that the maturational trends in the elimination processes described can be considered for other compounds (e.g., codeine) that undergo similar elimination routes.

Detection of an Endogenous Urinary Biomarker Associated With Cyp2D6 Activity Using Global Metabolomics

“…Studies conducted in the past two decades show major deficiencies with pediatric dosing methods built on allometry [4–8]. Optimal drug safety and efficacy in this vulnerable population requires an increased understanding of the impacts of physiological maturation and genetic variation on drug-metabolizing enzymes [9–11]. One such enzyme, CYP2D6, participates in the elimination of approximately 15% of clinically used drugs metabolized by cytochrome P450s [12], including antipsychotics and antidepressants, beta-blockers, opioid analgesics [13,14] and the antitussive dextromethorphan (DM) [15].…”

Efficacy of tramadol versus fentanyl for postoperative analgesia in neonates

“…In newborn infants, Mikhel'son et al 21 used tramadol for postoperative analgesia in 20 patients and reported adequate pain control. The analgesic efficacy of tramadol is partly dependent on its CYP2D6 -induced- O -desmethyl metabolite that exhibits an age-dependent maturation pattern 22. Therefore, CYP2D6 polymorphisms could possibly interfere in the pharmacological action of tramadol on studied infants, and at least 19 different alleles and 5 allele duplications have been already identified in African and European Brazilians 23.…”

Recent examples on the clinical relevance of the CYP2D6 polymorphism and endogenous functionality of CYP2D6

“…Age CYP2D6 seems to be functional already in first 2 weeks after birth [85][86][87] and seems generally not to decline substantially with older age; however, definite information is relatively sparse [88,89]. The article by Doki et al [89] found an interesting dependence of the age-related decline in flecainide clearance from the CYP2D6 genotype.…”