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Clinical Trial
. 1999 Jul;48(1):37-42.
doi: 10.1046/j.1365-2125.1999.00948.x.

Morphine and morphine-6-glucuronide in the plasma and cerebrospinal fluid of children

R D Hain  1 , A Hardcastle, C R Pinkerton, G W Aherne
Affiliations
Clinical Trial

Morphine and morphine-6-glucuronide in the plasma and cerebrospinal fluid of children

R D Hain et al. Br J Clin Pharmacol. 1999 Jul.

Abstract

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.

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Figures

Figure 1
Figure 1
Concentration of morphine in plasma (ng ml−1) following administration of morphine to children with leukaemia. —predicted concentrations, ○ =observed concentrations.
Figure 2
Figure 2
Comparison of (a) morphine concentrations in plasma and CSF. (b) morphine-6-glucuronide concentrations in plasma and CSF. (c) morphine and M6G concentrations in plasma. (d) morphine and M6G concentrations in CSF. • =plasma morphine, ▾ =CSF morphine, ○ =plasma M6G, x =CSF M6G.
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