Pharmacokinetic and pharmacodynamic study of morphine and morphine 6-glucuronide after oral and intravenous administration of morphine in children with cancer.
The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of morphine and morphine 6-glucuronide (M6G) in children with cancer. Serum concentrations of morphine and M6G in children who received single oral or short term continuous intravenous morphine were determined by HPLC and ELISA assays, respectively. The serum C(max) of morphine and M6G after i.v. morphine administration was 560.5 and 309.0 nM and the T(max) was 61 and 65 min, respectively. The elimination half-life was 140.0 and 328.7 min, respectively. After oral administration of morphine, the serum C(max) of morphine and M6G was 408.34 and 256.3 nM and the T(max) was 40.0 and 60 min, respectively. The half-life was 131.0 and 325.8 min, respectively. The side effects were: drowsiness (100%), nausea and/or vomiting (57%), pruritus (28%) and urinary retention (14%). There were no reports of respiratory complications. This study showed that pharmacokinetics factors of morphine and M6G in children were significantly different from adults. Therefore the required dose for children should be different from that of adults and should be based on studies performed on children rather than on studies on adults. Some adverse effects, particularly nausea and pruritus, may be commoner than is usually thought, while others, particularly respiratory problems did not occur.
Mashayekhi
Simin O
SO
Faculty of Pharmacy, NPMC and Haematology and Oncology Research Centre, Tabriz University (Medical Sciences), Tabriz, Iran.
Ghandforoush-Sattari
Mohammadreza
M
Routledge
Philip A
PA
Hain
Richard D W
RD
D000284:Administration, Oral; D000293:Adolescent; D001711:Biotransformation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000097:blood / Q000493:pharmacokinetics*; D009294:Narcotics / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D010147:Pain Measurement; D011537:Pruritus / Q000139:chemically induced; D012894:Sleep Stages / Q000187:drug effects; D016055:Urinary Retention / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
D009022:Morphine Derivatives; D009294:Narcotics; C035349:morphine-6-glucuronide; D009020:Morphine