Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions

1 The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants (24-41 weeks gestation) who were given a loading dose of 50 mu g kg(-1) or 200 mu g kg(-1) of diamorphine followed by an intravenous infusion of 15 mu g kg(-1) h(-1) of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2 Following both the 50 mu g kg(-1) or 200 mu g kg(-1) loading doses the mean steady-state plasma concentration (+/-s.d.) (sic) morphine, M3G and M6G were 86 +/- 52 ng ml(-1), 703 +/- 400 ng ml(-1) and 48 +/- 28 ng ml(-1) respectively and morphine clearance was found to be 4.6 +/- 3.2 ml min(-1) kg(-1). 3 M3G formation clearance was estimated to be 2.5 +/- 1.8 ml min(-1) kg(-1), and the formation clearance of M6G was estimated to be 0.46 +/- 0.32 ml min(-1) kg(-1). 4 M3G metabolite clearance was 0.46 +/- 0.60 ml min(-1) kg(-1), the elimination half-life was 11.1 +/- 11.3 h and the volume of distribution was 0.55 +/- 1.13 l kg(-1). M6G metabolite clearance was 0.71 +/- 0.36 ml min(-1) kg(-1), the elimination half-life was 18.2 +/- 13.6 h and the volume of distribution was 1.03 +/- 0.88 l kg(-1). 5 No significant effect of the loading dose (50 mu g kg(-1) or 200 mu g kg(-1)) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6 We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7 M3G:morphine and M6G:morphine steady-state plasma concentration ratios were 11.0 +/- 10.8 and 0.8 +/- 0.8, respectively. 8 The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults.