Hoskin, Peter John;
(1990)
Clinical and pharmacological aspects of the use of morphine in advanced cancer.
Doctoral thesis (M.D.), University College London.
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Abstract
The pharmacology of morphine has been studied with particular reference to its use in chronic dosage in patients with advanced cancer and to explore the hypothesis that one of its metabolites, mcxqphine-6-glucuronide, which is a highly potent analgesic in animal models, may play an important part in the analgesic action of morphine. In this work two different assays for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) have been compared; radioimmunoassay (RIA) and high performance liquid chromatography (HPLC). Basic pharmacokinetic parameters for morphine and morphine-6- glucuronide have been established in healthy volunteers. Changes in both morphine and M6G plasma concentrations were found to reflect changes in scores for drowsiness, relaxation and dry mouth after oral and intravenous administration. In cancer patients receiving regular doses of oral morphine there was a mean absolute bioavailability of 34% which was not significantly different from that in healthy volunteers. No influence of impaired hepatic function due to metastases was seen on this or plasma clearance. A ratio of morphine:M6G of between 1:6 and 1:9 was found (compared to a ratio of 1:11 in healthy volunteers), and the ratio of mco:phine:M3G was 1:55. The pharmacology of controlled release morphine tablets (MST- Continus) has been investigated. No difference in bioavailability relative to aqueous morphine solution was found and when changing from oral morphine solution to MST no advantage in using a loading dose of aqueous morphine when initiating treatment with controlled release tablets was found. Morphine, M3G and M6G have been demonstrated in CSF, pleural fluid and ascitic fluid from cancer patients. Evidence for an enterohepatic circulation of morphine has been obtained by the demonstration of these substances in bile from cancer patiaits receiving regular morphine. Patterns of use of morphine in patients with cancer pain have been studied by both a retrospective review of drug use in a continuing care unit and a postal questionnaire to a cross section of medical practitioners.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D. |
| Title: | Clinical and pharmacological aspects of the use of morphine in advanced cancer. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis Digitised by Proquest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10123274 |
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