Abstract
Preclinical drug absorption, distribution, metabolism and excretion studies, collectively referred to as drug disposition studies, are of fundamental importance to the interpretation and rationalisation of animal pharmacology and toxicology data, and the extrapolation of these data to humans. An assessment of the exposure of animals and humans to a drug and its metabolites must be made on a more scientific basis than can be provided by simply comparing dosage levels. Dose alone is not a satisfactory index of exposure, especially when comparing across species, since the same dose may result in very different levels of exposure because of species variations in drug disposition, particularly variations in metabolism. Not only is the disposition of a drug species-dependent, but also a number of physiological, pathological, genetic and environmental factors are now known to influence the disposition of drugs in the same individual or population (Bousquet, 1970; Smith, 1988).
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References
Aliens, E. J. (1966). Receptor theory and structure-action relationships. Adv. Drug Res., 3, 235–85
Bousquet, W. F. (1970). In Swarbrick, J. (Ed.), Current Concepts in the Pharmaceutical Sciences: Biopharmaceutics. Lea and Febiger, Philadelphia, pp. 151–95
Clark, B. and Smith, D. A. (1984). Pharmacokinetics and toxicity testing. CRC Crit. Rev. Toxicol., 12, 343–85
Chignell, C. F. (1977). In Garrett, E. R. and Hirtz, J. L. (Eds.), Drug Fate and Metabolism, Volume 1. Marcel Dekker, New York, pp. 187–228
Conney, A. H. (1971). In LaDu, B. N., Mandel, H. G. and Way, E. L. (Eds.), Fundamentals of Drug Metabolism and Drug Disposition. Williams and Wilkins, Baltimore, pp. 253–78
Davidson, C. (1971). In LaDu, B. N., Mandel, H. G. and Way, E. L. (Eds.), Fundamentals of Drug Metabolism and Drug Disposition. Williams and Wilkins, Baltimore, pp. 63–75
Drug Research Board, National Academy of Sciences/National Research Council (1969). Application of metabolic data to the evaluation of drugs. Clin. Pharmacol. Ther., 10, 607–34
EEC Commission (1980). Proposal for a council recommendation concerning tests relating to the placing on the market of proprietary medicinal products, Off. J. Eur. Communities, No. C355/6-29
Glockin, V. C. (1982). General considerations for studies of the metabolism of drugs and other chemicals. Drug Metab. Rev., 13, 929–39
Goldenthal, E. I. (1968). FDA papers, May 3, 1968, U.S. Food and Drug Administration, Washington, D.C.
Hansch, C. and Clayton, J. M. (1973). Lipophilic character and biological activity of drugs. II. The parabolic case. J. Pharm. Sci., 62, 1–21
Hirom, P. C., Millburn, P. and Smith, R. L. (1976). Bile and urine as complementary pathways for the excretion of foreign organic compounds. Xenobiotica, 6, 55–64
Kaplan, S. A. (1973). In Swarbrick, J. (Ed.), Current Concepts in the Pharmaceutical Sciences: Dosage Form Design and Bioavailability. Lea and Febiger, Philadelphia, pp. 1–30
Lake, B. G. and Gangolli, S. D. (1981). In Jenner, P. and Testa, B. (Eds.), Concepts in Drug Metabolism, Part B, Marcel Dekker, New York, pp. 167–218
Levine, W. G. (1983). In Caldwell, J. and Jakoby, W. B. (Eds.), Biological Basis of Detoxication. Academic Press, New York, pp. 251–85
Mertel, H. E. (1979). In Garrett, E. R. and Hirtz, J. L. (eds.), Drug Fate and Metabolism, Volume 3, Marcel Dekker, New York, pp. 133–91
Pang, K. S. (1983). In Caldwell, J. and Jakoby, W. B. (Eds.), Biological Basis of Detoxication. Academic Press, New York, pp. 213–50
Plaa, G. L. (1971). In LaDu, B. N., Mandel, H. G. and Way, E. L. (Eds.), Fundamentals of Drug Metabolism and Drug Disposition. Williams and Wilkins, Baltimore, pp. 131–45
Renwick, A. G. (1983). In Caldwell, J. and Jakoby, W. B. (Eds.), Biological Basis of Detoxication. Academic Press, New York, pp. 151–79
Smith, R. L. (1988). The role of metabolism and disposition studies in the safety assessment of pharmaceuticals. Xenobiotica, 18, 89–96
Trevor, A., Rowland, M. and Way, E. L. (1971). In LaDu, B. N., Mandel, H. G. and Way, E. L. (Eds.), Fundamentals of Drug Metabolism and Drug Disposition, Williams and Wilkins, Baltimore, pp. 369–99
Waddell, W. J. and Marlowe, C. (1977). In Garrett, E. R. and Hirtz, J. L. (Eds.), Drug Fate and Metabolism, Volume 1, Marcel Dekker, New York, pp. 1–25
Williams, R. T. (1971). In LaDu, B. N., Mandel, H. G. and Way, E. L. (Eds.), Fundamentals of Drug Metabolism and Drug Disposition, Williams and Wilkins, baltimore, pp. 187–205
World Health Organization (1966). Principles for pre-clinical testing of drug safety. World Health Organization Technical Report Series, 341
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Adams, W.J. (1990). The Metabolic Background. In: O’Grady, J., Linet, O.I. (eds) Early Phase Drug Evaluation in Man. Palgrave, London. https://doi.org/10.1007/978-1-349-10705-6_3
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DOI: https://doi.org/10.1007/978-1-349-10705-6_3
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