By T.A. Baillie
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Extra resources for Stable Isotopes: Applications in Pharmacology, Toxicology and Clinical Research
Sample text
This will, of course, result in an observable effect only where X-H(D) fission is rate-determining. There is an extensive literature on deuterium isotope effects in biological systems, and for a review of this topic, and its relevance in drug metabolism, reference may be made to Blake, Crespi and Katz (1975). Kinetic effects are normally expressed in terms of a ratio of rate constants, kH/kD' and for primary isotope-effects (X-H or D cleavage), these are generally in the range 2-5. Higher values have been observed, and, on theoretical grounds, a kH/kD ratio approaching lOis considered to be the maximum.
NAPA) 3C was administered intravenously while the unlabelled compound was taken orally and concentrations of both were then measured in plasma using a deuterated analogue, NAPA-d s , as the internal standard. 12 shows the plasma concentrations obtained in one such study in man, and a detailed pharmacokinetic analysis of these and of related data has been reported. A key observation was that oral absorption of NAPA was approximately 85 per cent, adequate for therapeutic purposes and similar to that for procainamide itself.
And Dollery, C. T. (1976). Advances in Mass Spectrometry in Biochemistry and Medicine, Vol. 2 (ed. A. Frigerio), Spectrum Publications, New York, p. 389 Draffan, G. , Gilbert, J. D. and McGregor, J. S. (1977). Unpublished observations Falkner, F. , Sweetman, B. J. and Watson, J. T. (1975). Appl. Spectrosc. , 10,51 Garland, W. , Trager, W. F. and Nelson, S. D. (1974). Biomed. , Holmstedt, B. and Ryhage, R. (1968). Anal. , Tang, B. K. and Kalow, W. (1976). Proceedings of the Second International Conference on Stable Isotopes (ed.