Cerebrospinal fluid and plasma pharmacokinetics of morphine infusions in pediatric cancer patients and rhesus monkeys.
The cerebrospinal fluid (CSF) and plasma pharmacokinetics of morphine administered as a continuous infusion were studied in pediatric cancer patients and in monkeys with implanted Ommaya reservoirs. In monkeys administered a constant infusion of 0.15 mg morphine sulfate/kg/h, morphine steady-state plasma and CSF concentrations were 84.4 +/- 20.0 ng/ml and 25.3 +/- 4.9 ng/ml, respectively, for a CSF:plasma ratio of 0.30 +/- 0.05. For comparison, the monkeys also received morphine as an intravenous bolus at a dose of 0.45 mg morphine sulfate/kg. The CSF:plasma area under the concentration-time curve (AUC) ratio was 0.40 +/- 0.07, similar to that seen with continuous infusion. Morphine pharmacokinetics were also studied in cancer patients administered long-term infusions of morphine sulfate over a wide dosage range (0.04-31 mg/kg/h). The steady-state plasma concentration of morphine was linearly related to the infusion rate although variability was noted. The average clearance value was 23 ml/min/kg which is at the upper end of the estimates reported for morphine clearance using bolus administration. No evidence for morphine accumulation using long-term administration was observed. A limited number of CSF samples obtained by lumbar puncture showed comparable CSF and plasma concentrations of unbound morphine assuming morphine is approximately 30% bound in human plasma.
Greene
Raymond F
RF
Department of Pharmacology, George Washington University Medical Center, Washington, DC, USA Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 U.S.A. Pediatrie Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 U.S.A.
Miser
Angela W
AW
Lester
Cindy M
CM
Balis
Frank M
FM
Poplack
David G
DG
D000818:Animals; D001693:Biological Transport, Active; D002648:Child; D006801:Humans; D007262:Infusions, Intravenous; D008253:Macaca mulatta; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*
D009020:Morphine