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 μg kg −1 or 200 μg kg −1 of diamorphine followed by an intravenous infusion of 15 μg 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 μg kg −1 or 200 μg kg −1 loading doses the mean steady‐state plasma concentration (±s.d.) of 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 μg kg −1 or 200 μg 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.