Related Experiment Videos
Morphine and morphine-6-glucuronide in the plasma and cerebrospinal fluid of children
R D Hain1, A Hardcastle, C R Pinkerton
1Departments of Paediatric Oncology and Palliative Care, Llandough and Community NHS Trust, Penlan Road, Cardiff CF64 2XX, UK.
Insights
Children with cancer extensively metabolize morphine to morphine-6-glucuronide (M6G). This study measured morphine and M6G in pediatric plasma and cerebrospinal fluid, highlighting M6G
Area of Science:
- Pediatric pharmacology
- Pharmacokinetics
- Cancer pain management
Background:
- Morphine is a common analgesic in children.
- Understanding morphine metabolism is crucial for safe and effective pain management.
- Morphine-6-glucuronide (M6G) is an active metabolite with potential for accumulation.
Purpose of the Study:
- To quantify morphine and M6G concentrations in pediatric plasma and cerebrospinal fluid (CSF).
- To characterize the pharmacokinetics of morphine and M6G in children with leukemia.
- To compare morphine and M6G passage into the CSF of children versus adults.
Main Methods:
- Collected paired plasma and CSF samples from 29 children with leukemia undergoing lumbar puncture.
- Administered a single intravenous dose of morphine prior to sample collection.
- Measured morphine using radioimmunoassay (RIA) and M6G using enzyme-linked immunosorbent assay (ELISA).
Main Results:
- ELISA for M6G demonstrated high sensitivity and acceptable assay variability.
- Pediatric morphine pharmacokinetics (elimination half-life, volume of distribution) were comparable to adults, but clearance was higher.
- Children readily synthesized M6G, which had a significantly longer elimination half-life and higher area under the curve (AUC) in plasma compared to morphine.
Conclusions:
- Demonstrated extensive morphine metabolism to M6G in pediatric cancer patients.
- Results support the clinical significance of M6G accumulation with repeated morphine dosing in children.
- No evidence suggested increased morphine penetration into the CSF of children compared to adults.
Aims:
To measure morphine and morphine-6-glucuronide in the plasma and cerebrospinal fluid of children following a single intravenous dose of morphine.
Methods:
Twenty-nine paired samples of cerebrospinal fluid and plasma were collected from children with leukaemia undergoing therapeutic lumbar puncture. An intravenous dose of morphine was administered at selected intervals before the procedure. Concentrations of morphine and morphine-6-glucuronide (M6G) were measured in each sample. Morphine was measured using a specific radioimmunoassay (r.i.a.) and M6G was measured using a novel enzyme-linked immunosorbent assay (ELISA).
Results:
The ELISA for measuring M6G was highly sensitive. The intra-and interassay variations were less than 15%. Using a two-compartment model for plasma morphine, the area under the curve to infinity (AUC, 7143 ng ml-1 min), volume of distribution (3.6 l kg-1 ) and elimination half-life (88 min) were comparable with those reported in adults. Clearance (35 ml min-1 ) was higher than that in adults. Morphine-6-glucuronide was readily synthesized by the children in this study. The elimination half-life (321 min) and AUC (35507 ng ml-1 min) of plasma M6G were much greater than those of morphine.
Conclusions:
Extensive metabolism of morphine to M6G in children with cancer has been demonstrated. These data provide further evidence to support the importance of M6G accumulation after multiple doses. There was no evidence that morphine passed more easily into the CSF of children than adults.