Morphine kinetics after diamorphine infusion in premature neonates.

Abstract

1. The pharmacokinetics of morphine were studied in 26 newborn premature neonates (26‐38 weeks gestational age) who were given a loading dose of 50 micrograms kg‐1 of diamorphine followed by an intravenous infusion of 15 micrograms kg‐1 h‐1 of diamorphine. Plasma concentrations of morphine were measured during the infusion at steady‐ state and for 24 h after the cessation of the diamorphine infusion. 2. The mean steady‐state plasma morphine concentration (+/‐ s.d.) for a diamorphine infusion rate of 15 micrograms kg‐1 h‐1 was 62.5 +/‐ 22.8 ng ml‐1. 3. Morphine clearance was 3.6 +/‐ 0.9 ml min‐1 kg‐1, the elimination half‐life was 8.9 +/‐ 3.3 h and the volume of distribution was 2.7 +/‐ 1.01 kg‐1. 4. Morphine elimination kinetics were described by a mono‐exponential function. 5. There was a direct relationship between the gestational age of the patients and the clearance (r2 = 0.31, P = 0.003) and half‐life (r2 = 0.35, P = 0.01) of morphine, but no relationship was found between gestational age and volume of distribution. 6. The results suggest that the currently used dosing regimen of diamorphine achieves a safe and effective morphine concentration in the premature newborn but that the loading dose could be modified to achieve a more rapid onset of analgesia. 1991 The British Pharmacological Society