Metabolism and excretion of phenothiazine tranquillisers by the horse

Weir, John J.R. (1970) Metabolism and excretion of phenothiazine tranquillisers by the horse. PhD thesis, University of Glasgow.

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Abstract

The historical development, uses, pharmacology, chemistry and metabolism of phanothiazine and the phenothiazine tranquillisers are reviewed along with the analytical techniques which have been used for their detection and determination.

The metabolism and excretion by the horse of promazine chlorpromazine, acepramazine and propionylpromazine, tranquillisers commonly used in equine practice, have been examined qualitatively and quantitatively. Methods of collection, storage and analysis of horse urine have been developed, and the use of mass spectroscopy in combination with gas liquid chromatography for the detection of phenothiazine derivatives in biological fluids has been examined.

Qualitative results have shown that many biotransformations of such derivatives take place in the horse. 30 metabolites of promazine were detected in addition to the parent drug, 20 of chlorpromazine and 11 and 6 respectively from acepromazine and propion ylpromazine. Hydroxylation followed by conjugation, prademinantly with glucoronic acid and to a smaller extent with sulphuric acid, is the major route of metabolism of promazine and chlorpromazine. Acapromazine and propionylpromezine, on the other hand, are not conjugated to a great extent. Instead they lose the side chain ketone grouping attached to the nucleus at the 2-position and are excreted in the sulphoxide form.

Quantitative results have shown that excretion is irregular and prolonged, in some cases lasting for a week after administration. The percentage of dose detected as urinary metabolites res low, being approximately 19% for chlorpromazine, 10% for promazine and 3% for acepromazine. Conjugated metabolites were excreted predominantly as sulphide derivatives, whereas the unconjugated fraction were predominantly in the sulphoxide form.

The applicability of the techniques used for the detection of phenothiazine derivatives, after administration in small doses just sufficient to produce an effect, has also been examined.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Veterinary medicine, horse, phenothiazine tranquillisers.
Subjects: S Agriculture > SF Animal culture > SF600 Veterinary Medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Supervisor's Name: Sanford, Dr. J.
Date of Award: 1970
Depositing User: Mrs Marie Cairney
Unique ID: glathesis:1970-30711
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jul 2018 14:31
Last Modified: 30 Jul 2018 14:34
URI: http://theses.gla.ac.uk/id/eprint/30711

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