Morphine kinetics after diamorphine infusion in premature neonates.
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.
Barrett
D A
DA
Department of Pharmaceutical Sciences, Nottingham University.
Elias-Jones
A C
AC
Rutter
N
N
Shaw
P N
PN
Davis
S S
SS
D001724:Birth Weight; D002851:Chromatography, High Pressure Liquid; D005865:Gestational Age; D006207:Half-Life; D003932:Heroin / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D007262:Infusions, Intravenous; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000097:blood / Q000493:pharmacokinetics*; D011863:Radioimmunoassay
D003932:Heroin; D009020:Morphine