Isotopes, stable pharmacology

TR Browne. Stable isotopes in pharmacological studies present and future. J Clin Pharmacol 26 485 189, 1986. 

Browne, T.R., Stable isotopes in pharmacology studies Present and future, J. Clin. 

Baillie, T.A., Stable Isotopes Application in Pharmacology, Toxicology and Clinical Research, Macmillan, London, 1978. 

Guinn, V, P, Activation Analysis with Particular Attention to the Detection of Stable Tracers. In Isotopes in Experimental Pharmacology (L.J. Roth, Ed.). Chicago University of Chicago Press 1965. 

De Ridder, J. J., and Koppens, P. C. (1978). Discrimination between endogenous and exogenous testosterone in human plasma after oral treatment with testosterone undecano-ate, using stable-isotope labeled compounds and mass spectrometric analysis. In Stable Isotopes. Applications in Pharmacology, Toxicology and Clinical Research (T. A. Baillie, ed.), pp. 157-165. Mcmillan, New York. 

Klein, P.D., Hachey, D.L., Kreek, M.J., and Schoeller, D.A. In. T. A. Balllle. (ed). "Stable Isotopes Applications in Pharmacology, Toxicology and Clincal Research" University Park Press, Baltimore, 1978, p. 3-14. 

While adequate Intestinal absorption Is clearly required to maintain zinc sufficiency, a number of different methods are presently used for Its measurement. Intestinal absorption has been measured by clinical balance studies, tracers (using both stable and radioactive Isotopes) and serum levels after Ingestion of pharmacologic doses of stable zinc compounds. Each can be useful, but each also has limitations and It Is Important to note that different methods. In reality, measure different aspects of absorption. While results are often reported as absorption, specific nomenclature has been developed to specify the results from each method of measurement(13,14). 

Proceedings of a Seminar on the Use of Stable Isotopes in Clinical Pharmacology, Chicago, Illinois, eds. P. D. Klein and L. J. Roth (National Technical Information Service, U.S. Department of Commerce—document code CONF-7I1115, 1971). 

This review is intended to survey those uses of stable isotopes which are of particular importance in medicinal chemistry. These include their use in 1) structure elucidation, 2) studies of drug metabolism, 3) pharmacokinetic analysis and 4) drugs used in therapy. The use of stable isotopes for investigating intermediary metabolism, and their rapidly expanding use in clinical chemistry will not be reviewed since these topics have been covered elsewhere. Synthesis and biosynthesis with stable isotopes have also been previously surveyed >10 and many articles appear in each issue of the Journal of Labelled Compounds and a few have appeared in Biomedical Mass Spectrometry in the past year. In addition, one recent article has appeared on the use of plants to continously produce stable isotope labeled compounds of pharmacological interest. ... 

In the fields of pharmacology, toxicology and medicine, Jellum [16] showed how GC/MS opened the door to new possibilities. His exhaustive work describes the problems associated with GC/MS, as well as those involved with the processing of the data obtained. The use of stable isotopes for these studies is a non-negligible contribution, as shown by Krahmer and McCloskey [17] during the development of this methodology. Klein and Klein [18,19] performed a veritable census of labeled molecules so far prepared for these analyses. 

Yan and his colleagues used a stable isotope labeled proteome internal standard to analyse protein expression alterations during oxidative stress in breast epithelial cells. Affinity chromatography was combined with MS/MS in the proteomic analysis of human 06-methylguanine-DNA methyltransferase. These studies demonstrated that proteomics can elucidate protein expre-ssions associated with the pharmacological and toxic effects of an anticancer drug when integrated with other biochemical methods. 

Since the 1977 review in Annual Reports, the applications of stable-isotope-labeled compounds to biomedical research have increased dramatically. Three international conferences devoted to the use of stable isotopes in the life sciences and one to synthesis and general applications have been held. Review articles have focused on mass spectrome-tric-based analytical methods, on applications of stable isotopes in clinical and pharmacological research, and on more specific studies concerning problems in drug metabolism, pharmacokinetics and synthesis. The present review covers mainly the literature published since 1981 and focuses on recent developments in the use of stable isotopes for investigations of drug metabolism and disposition. 

Matwiyoff, N. A. Walker, T. E. "Trends in the Use of Stable Isotopes in Biochemistry and Pharmacology" in Stable Isotopes in the Life Sciences (Proc. Symp. Leipzig, 1977) IAEA,... 

Baillie TA and Rettenmeier AM (1986) Recent advances in the use of stable isotopes in drug metabolism research. Journal of Clinical Pharmacology 26(6) 481—484. 

Symposium on Stable Isotopes Applications in Pharmacology, Toxicology, and Clinical Research, Royal Postgraduate Medical School, London, 1977, to be published. 

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