Pharmacokinetic and pharmacodynamic study of morphine and morphine 6‐glucuronide after oral and intravenous administration of morphine in children with cancer

Abstract

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.

Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery

“…Dagan and colleagues (8) reported significantly lower clearance in children undergoing the Fontan procedure The morphine steady-state volume of distribution that we observed in this study, 7.3 L/kg, is closer to values reported in cancer patients (35) and patients receiving mechanical ventilation (6,18), 5 L/kg, than to the value reported in post-cardiac surgery patients (8), 13 L/kg. Similar to clearance, distribution volume is not influenced by cardiovascular status.…”

The development of a high-performance liquid chromatography–tandem mass spectrometric method for simultaneous quantification of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine in serum

“…Therefore, expected concentrations of morphine and its glucuronides would be around 50-100 ng/mL or lower. [17, 18] We decided to extend the ULOL to a reasonable level for future studies.…”

Auditing Analgesic Use in Post-operative Setting in a Teaching Hospital

“…It can also lead to complications like deep vein thrombosis, atelectesis and also delayed wound healing [2]. The other concern in inadequate pain relief is the fear of the possibility of development of physical dependence, tolerance and addiction with the use of opioid analgesics [3]. Undertreated severe pain may have physiological consequences increasing the stress response to surgery, seen as a cascade of endocrine-metabolic and inflammatory events that ultimately may contribute to organ dysfunction, morbidity, increased hospital stay and mortality.…”