Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P-450 2D6 activity

Maturational clearance of tramadol is almost complete by 44 weeks PCA. A target concentration of 300 µg litre−1 is achieved after a bolus of tramadol hydrochloride 1 mg kg−1 and can be maintained by infusion of tramadol hydrochloride 0.09 mg kg−1 h−1 at 25 weeks PCA, 0.14 mg kg−1 h−1 at 30 weeks PCA, 0.17 mg kg−1 h−1 at 35 weeks PCA, 0.18 mg kg−1 h−1 at 40 weeks, 0.19 mg kg−1 h−1 at 50 weeks PCA to 1 yr, 0.18 mg kg−1 h−1 at 3 yr and 0.12 mg kg−1 h−1 in adulthood. CYP2D6 activity was observed as early as 25 weeks PCA, but the impact of CYP2D6 polymorphism on the variability in pharmacokinetics, metabolism and pharmacodynamics of tramadol remains to be established.