Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.277698
Title: Analysis and pharmacokinetics of morphine and morphine-6-glucuronide
Author: Chapman, David John
ISNI:       0000 0001 3528 9594
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1990
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Abstract:
The behaviour of morphine and morphine glucuronides has been defined in an attempt to overcome the confusion surrounding the pharmacokinetics of morphine and the potential contribution of the active metabolite morphine-6-glucuronide (M6G), to the clinical effects observed after morphine treatment. Differential RIAs for the quantitation of morphine, M6G, and morphine-3-glucuronide (M3G) in a range of biological fluids have been developed. A specific M6G antiserum, suitable for use in an immunoassay, has been successfully raised. Pharmacokinetic parameters for morphine and M6G have been established in volunteers treated with morphine. Similar quantities of morphine and M6G were. observed after intravenous dosing. Bioavailabilities of enteral morphine preparations ranged between 19% and 24%. There was little difference between these routes with respect to the relative quantities of morphine and M6G measured, with quantities of M6G exceeding those of morphine by up to 7-fold. Data obtained following intravenous morphine, or M6G revealed similar elimination half-lives for both compounds. M6G was less widely distributed and not significantly bound by plasma proteins. Significant biliary concentrations of morphine and morphine glucuronides suggested the presence of an enterohepatic circulation, but no secondary plasma peaks or prolonged elimination half-lives were apparent. After systemic administration, significantly less M6G than morphine entered the central nervous system (CNS). In rats, the mean brain:serum ratios for morphine and M6G were 0.4:1 and 0.2:1 respectively. A mean cerebrospinal fluid (CSF):plasma morphine ratio of 0.9:1 was found in patients receiving intravenous morphine; no M6G was detected in the CSF. After oral morphine, mean CSF:plasma ratios were 0.6:1 and 0.3:1 for morphine and M6G respectively. A similar rate of disappearance from the CNS was observed for both morphine and M6G. Following intravenous M6G, the mean M6G CSF:plasma ratio was 0.1:1. Morphine was absent from the CSF and plasma indicating that the clinical effects observed are due to M6G alone.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.277698  DOI: Not available
Keywords: Pharmacology & pharmacy & pharmaceutical chemistry
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