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

Aims To measure morphine and morphine-6-glucuronide in the plasma and cereb rospinal fluid of children following a single intravenous dose of morphine. Methods Twenty-nine paired samples of cerebrospinal fluid and plasma were c ollected from children with leukaemia undergoing therapeutic lumbar punctur e. An intravenous dose of morphine was administered at selected intervals b efore 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 int erassay variations were less than 15%. Using a two-compartment model for pl asma morphine, the area under the curve to infinity (AUC, 7143 ng ml(-1) mi n), volume of distribution (3.61 kg(-1)) and elimination half-life (88 min) were comparable with those reported in adults. Clearance (35 ml min(-1)) w as higher than that in adults. Morphine-6-glucuronide was readily synthesiz ed by the children in this study. The elimination half-life (321 min) and A UC (35507 ng ml(-1) min) of plasma M6G were much greater than those of morp hine. 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.