Pharmacokinetics of morphine infusion in premature neonates.
Morphine pharmacokinetics were studied in 17 premature neonates (26-34 weeks' gestation) after intravenous infusion during the first 24 hours of life. Infants received either standard dose morphine that comprised of a 100 micrograms/kg/hour loading infusion for 2 hours followed by a maintenance infusion of 12.5 micrograms/kg/hour, or a high dose of 200 micrograms/kg/hour for 2 hours followed by 50 micrograms/kg/hour. Mean plasma concentrations of morphine (SD) after 2 and 24 hours were 99 (12.9) and 96.4 (3.2) ng/ml, and 184.2 (37.7) and 319 (71.2) ng/ml for the standard and high dose regimens, respectively. Morphine-3-glucuronide plasma concentrations achieved about 20% and 80% of morphine values at 2 and 24 hours respectively. Morphine-6-glucuronide could not be detected at 2 hours, but attained 20-25% of morphine plasma concentrations by 24 hours. The population mean morphine clearance was 2.4 ml/min/kg, the elimination half life was 8.75 hours and the volume of distribution was 1.82 1/kg. High plasma concentrations of morphine appeared to be well tolerated. Although mean arterial blood pressure decreased during the first six hours of treatment, this was not statistically significant; two infants experienced transient muscle rigidity, but no evidence of seizures was noted. There appears to be no clinical advantage in using the high dose regimen.
Hartley
R
R
Department of Clinical Medicine, University of Leeds.
Green
M
M
Quinn
M
M
Levene
M I
MI
D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000378:metabolism* / Q000628:therapy; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000097:blood / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000097:blood; D012121:Respiration, Artificial
D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide