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|  | The pharmacokinetics & metabolism of Ergot Alkaloids: the contribution made by immunoassays |
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| Ergot alkaloid derivatives are very widely prescribed in therapeutics. They are indicated in the basic treatment of migraine and vascular headaches, in the behavioural problems of old age, in Parkinson's Disease and in hyperprolactinemia. Because of their high levels of activity, they are administered in very small doses. Consequently, plasma levels are always very low, particularly as they are thoroughly metabolised. |
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| The choice of analytical method for these compounds is the key factor in the success of pharmacokinetic studies. We have developed immunoassay methods (RIA or EIA) for the principal derivatives of ergot alkaloids and their metabolites. These methods are both sensitive and specific. Their advantages are illustrated by two examples taken from research undertaken in our laboratories. |
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| An original strategy has been developed to determine the specificity of the antibodies produced. Two populations of antibodies were thus isolated, one specific to the molecule before metabolism and the other specific to all the metabolites. |
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| This made it possible to monitor an active principle and its metabolites separately for a period of more than 24 hours after administration of therapeutic doses to human beings or to animals. This strategy was applied to all the substances listed in the box. |
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| These analytical methods have, for example, made it possible to study the drug interaction of macrolide anti-biotics such as troleandomycin (TAO) with dihydroergotamine. |
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| This study was carried out in vitro on hepatic micro-somes after treatment of rats with TAO. It was demonstrated in this way that the formation of macrolide-cytochrome P-450 complex led to inhibition of the fixation of dihydroergotamine with cytochrome P-450 and of its metabolism. J.-M. G. |
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