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Title: The biochemistry and pharmacokinetics of some endogenous and synthetic glucocorticoids
Author: Tredger, John Michael
ISNI:       0000 0001 3536 1760
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1973
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Various aspects of the pharmacokinetics of endogenous and synthetic glucocorticoids have been examined in an attempt to understand the prolonged physiological effects of the synthetic steroids, and to characterise their metabolic fate. The biochemical interactions of these compounds with the hepatic mixed-function oxygenase system have also been studied, and this enzyme complex has been used to resolve the mediating factors in the expression of circadian rhythms. The results have demonstrated that betamethasone and dexamethasone are metabolised primarily by hydroxylation in both rat and guinea pig, and that this occurs less rapidly than does the reductive metabolism of the endogenous corticosteroids. The hepatic clearance of the synthetic glucocorticoids is also slower than that of corticosterone, and this, by virtue of their prolonged tissue retention, may contribute towards the greater biological potency of the synthetic analogues. Glucocorticoids influence hepatic drug metabolism, largely by their effects on the levels of cytochrome P-450 and the rate of its reduction. Such changes seem to result from effects on protein synthesis, but other phenomena, possibly allosteric in nature, appear important. It seems likely that the same glucocorticoid mediated effects may be responsible for expression of the observed diurnal rhythms in drug metabolism and steroid metabolism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available