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A Michalkiewicz

Publications and source records attributed to A Michalkiewicz.

5 recordsLinked to original sources
PubMed1992

Differential inhibition of hepatic morphine UDP-glucuronosyltransferases by metal ions.

The major metabolites of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), possess significant pharmacological properties. Whilst both metabolites bind to mu-opioid binding sites, M6G is a potent agonist whereas M3G antagonizes some of the effects of morphine and M6G. An inter-species comparison of in vitro hepatic morphine processing was performed. The results showed that not all species were able to produce M6G whereas all those tested did produce M3G. Guinea-pig liver produced the greatest amounts of M6G and was therefore chosen as a model to study morphine glucuronidation in further detail. Inclusion of the detergent Brij 58 (0.33 mg/mg protein) and Mg2+ (15 mM) in the standard assay incubation gave optimal production of both M3G and M6G by guinea-pig liver homogenates. A number of metal ions were investigated for their ability to inhibit glucuronidation of morphine in both the 3- and 6-positions. Some metal ions, namely Cu+, Cu2+ and Cd2+, were able to inhibit the production of M3G without affecting glucuronidation at the 6-position. Taken together, these data provide further evidence for the existence of UDP-glucuronosyltransferase isoenzymes responsible for the metabolism of morphine. In addition these isoenzymes can be differentially modulated and therefore it is possible to alter the ratio of M3G:M6G formed during in vitro metabolic studies.

Animals↗
PubMed1992

Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue.

Intra-articular morphine (5 mg in 25 ml) was administered to patients for post-operative analgesia following arthroscopic knee surgery. At various time intervals, 30 min to 4 h post morphine, venous blood samples were taken in order to determine plasma levels of morphine and its primary metabolites, morphine-3-glucuronide and morphine-6-glucuronide. Measurable amounts of morphine and morphine-3-glucuronide were found in the plasma of 7/10 patients whereas morphine-6-glucuronide was detected in only 2/10 patients. The plasma levels of morphine were lower than that regarded sufficient for post-operative analgesia in all but two patients, indicating a possibility of peripheral analgesia. In addition, synovial biopsy samples were assayed for the presence of opioid binding sites. Tissue samples from 11 different patients were analysed and 6/11 exhibited specific binding of [3H]naloxone, indicating the presence of opioid binding sites/receptors. The receptor type (i.e. mu-, delta- or k-) is at present unknown. Taken together, these data provide evidence that locally administered opiates can act on specific opioid receptors in the synovium to mediate analgesia.

Adult↗
PubMed1992

Morphine metabolism in neonates and infants.

The metabolism of morphine was studied in seven fullterm neonates and five infants receiving a continuous infusion of morphine. All the patients had detectable plasma concentrations of morphine 3-glucuronide (M3G) and 10 had detectable concentrations of morphine 6-glucuronide (M6G). The mean plasma clearance of morphine was 20.1 ml min-1 kg-1 in neonates and 23.4 ml min-1 kg-1 in the group as a whole. The M3G/morphine ratio (7.3) was higher than that previously reported for preterm neonates (5.0) but lower than that reported for children (23.9).

Chromatography, High Pressure Liquid↗
PubMed1990

Fast reliable assay for morphine and its metabolites using high-performance liquid chromatography and native fluorescence detection.

A method for the fast analysis of morphine (M), normorphine (NM), morphine-3- and -6-glucuronides (M3G and M6G) and codeine (C) is described which has the advantages of sensitivity, speed and specificity. Dihydrocodeine and heroin can also be assayed. The method is based on extraction of the opiates from serum, plasma and cerebrospinal fluid using reversed-phase solid-phase extraction columns, followed by reversed-phase high-performance liquid chromatography with native fluorescence detection. The extraction step provides greater than 95% recovery, and the response of the detection system is linear from 0.5 to beyond 750 ng. The method allows analysis of M, NM, M3G, M6G and C. No other drugs have been found to interfere with the assay. The assay offers a quick, cheap and reliable method of specifically determining morphine and its metabolites, including the potent M6G, from a small sample volume; this will be of advantage to both clinician and basic scientist.

Chromatography, High Pressure Liquid↗