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 | The contribution of stable isotopes to pharmacology |
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| One specific prerequisite for studying the pharmacology of molecules of biological interest is the ability to follow their evolution within the body. Molecules la-belled with stable (2H, 13C, 15N, 18O, 34S, etc...) or radioactive isotopes often have the advantage of possessing the same chemical structures as the molecules themselves. The use of stable isotopes has in-creased with analytical techniques (such as mas spectrometry, atomic emission spectro-metry and NMR) which make it possible to differentiate between labelled and non-labelled molecules. A number of pharmacokinetics and the metabolism of biological compounds are presented below. |
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| An endogenous molecule (steroid, amino acid, fatty acid, etc...) labelled with a stable isotope makes it possible to obtain either i) an internal standard for assay of the molecule in biological media, or ii) a marker to determine in the body the evolution of the molecule or, more accurately, of its active site. For example, the turnover of the protein is assessed by following the 15N/13N ratio within the protein over time after the administration of a precursor (amino acid) labelling with 15N. Second example: study of the catabolism of a fatty acid or a protein requires previous labelling so that the metabolites, such as CO2 in expired air (after labelling with 13C) or urinary urea (after labelling with 15N), can be determined. Finally, this approach can also be used to assess the effect of a drug on the metabolic cycle of endogenous products. |
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| Studying the pharmacokinetics of the exogenous form of a compound or element found naturally in man, requires the ability to differentiate between the two biological entities (endogenous and exogenous). This is achieved by labelling the exogenous compound with a stable isotope which distinguishes it from its endogenous homologue. SPI has measured the absolute bioavailability of an oral form of magnesium salt by administering this oral form enriched with a sta-ble isotope (26Mg) at the same time as a reference intravenous solution enri-ched with a second stable isotope of magnesium (25Mg). Thus, the two ma-gnesium isotopes administered orally and intravenously have been assayed simultaneously in the body. |
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| Stable isotopes also make it possible to identify me-tabolites of a non-labelled drug administered to man or animal. |
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| Treating the sample with a reagent able to derivatize one specific functional group and them treating the sample with a labelled homologue (deuterated, for example) makes it possible to determine the number of fixation sites of the reagent and to establish the structure of the metabolite. |
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| Stable isotopes are analytical markers which enable us to explain the biochemical and pharmacological mechanisms of endogenous or exogenous com-pounds. They provide an alternative to radioactive isotopes, which are subject to specific regulations and which may have short half-life. H.B |
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