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By Richard Lancaster (Auth.)

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Debrisoquine is a guanidinium hypotensive agent (see Chapter 23) that undergoes carbon oxidation in the liver to form a n u m b e r of phase 1 metabolites, of which the most important is 4-hydroxy-debrisoquine. When the ratio unchanged debrisoquine/4-hydroxy-debrisoquine in an 8 hour collection of urine is determined in the population, there is a bimodal frequency distribution, 9 1 % of the population rapidly metabolising the drug and having ratios of 0· 1-5, while the remaining 9 % have ratios of 20-300.

Parke, D. V. (1968), The metabolism of drugs. In Recent Advances in Pharmacology. ) 30-74. Churchill, London. Thomas, B. , Coldwell, Β. , Zeitz, W. and Solomonraj, G. (1972), Effect of aspirin, caffeine and codeine on the metabolism of phenacetamin and acetaminophen. Clin. Pharmacol, and Ther. 13, 906-910. Williams, R. T. (1974), Inter-species variations in the metabolism of xenobiotics. The Eighth CIBA Medal Lecture. Biochem. Soc. Trans. 2, 359-377 Chapter 4 Pharmacokinetics Pharmacokinetics is the study of the rates at which the various physical and chemical processes to which drugs are subjected in the body occur and of the relationship of these to the speed of onset, the intensity and the duration of drug effects.

F. (1973), The kidney as an endocrine organ for the production of 1,25-dihydroxy-vitamin D 3 , a calcium-mobilising hormone. New Engl. J. Med. 289, 359-365. , Schneeider-Deters, C. and Dengler, H. J. (1974), Influence of thyroid status on plasma half-life of antipyrine in man. New Engl. J. Med. 290, 1040-1042. Gillette, J. R. (1971), Factors affecting drug metabolism. Ann. Y. Acad. Sei. 179, 43-66. Gillette, J. , Michell, J. R. and Brodie, Β. B. (1974), Biochemical mechanisms of drug toxicity. Ann.

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