Concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured by h.p.l.c. in plasma and cerebrospinal fluid (CSF) samples from 16 patients with cancer receiving oral (controlled-release) morphine. There was a close correlation between plasma and CSF morphine concentrations (r = 0.94, P = 0.0001) and both correlated with drug dosage (r = 0.61, P = 0.013 and r = 0.74, P = 0.0001, respectively). M3G and M6G in plasma and CSF were correlated (r = 0.81 and r = 0.82, both P = 0.0001). No relationship was apparent between M plus M6G concentrations in the CSF and pain scores.
In ten patients who received an epidural injection of 15 mg of nicomorphine, the compound was relatively slowly released from the epidural space and was found in plasma for approximately 1.5 h. Nicomorphine is relatively slowly metabolized into 6-nicotinoylmorphine and morphine. The rate of release is patient-dependent. The relative AUC values are 15.3% for nicomorphine, 23.9% for 6-nicotinoylmorphine and 60.8% for morphine. The mean clinical effect lasts for 18.2 +/- 10.1 h.
SummaryAfter intravenous administration of 3,6-dinicotinoylmorphine (nicomorphine) 30, 20 and 10mg to patients undergoing surgery, this agent is rapidly metabolised into the metabolites 6-mononicotinoylmorphine (6MNM) and morphine. The elimination half-lives are 1 minute for nicomorphine, 13 minutes for 6MNM and 120 minutes for morphine. Morphine is subsequently metabolised into morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). The halflife of these 2 glucuronide conjugates is similar, about 225 minutes. A glucuronide conjugate of 6MNM was not detected. The area under the serum concentration-time curve of nicomorphine and its metabolites is linearly related to the dose.
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