Abstract
The dependence of the rates of oxidative metabolism of drugs and toxic chemicals on tissue oxygen concentration and hence on bodyweight is established. Consequences of this for species differences in the rates of deactivation of drugs and activation of toxic chemicals are considered, especially for the veterinary prescription of drugs and for the use of experimental animal models in the safety evaluation of drugs and chemicals. The high rate of oxidative activation of toxic chemicals in the mouse, the high level of hepatic cytochrome P-448, and the high potential for autoxidative tissue injury in this species, are considered to make it an inappropriate animal for chronic toxicity and carcinogenicity studies.
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References
Berry, D.J. 1982. The disposition and pharmacokinetics of feprazone in human subjects, Ph.D. Thesis, University of Surrey.
Breacker, P.J., Ioannides, C., Taylor, I. and Parke, D.V. 1982. Species differences and rates of mixed-function, oxidation. Proceedings Fifth International Symposium on Microsomes, and Drug Oxidations, Tokyo 1981, in press.
Brown, D.M., Langley, P.F., Smith, D. and Taylor, D.C. 1974 Metabolism of chloroform. I. The metabolism of14C-chloroform by different species. Xenobiotica, 4: 151–163.
Booth, J., Boyland, E. and Cooling, C. 1967. The respiration of human liver tissue. Biochem. Pharmac., 16: 721–724.
Chatfield, D.H. and Green, J.N. 1978. Disposition and metabolism of benoxaprofen in laboratory animals and man. Xenobiotica 8: 133–144.
Creaven, P.J., Parke, D.V. and Williams, R.T. 1965. A fluorimetric study of the hydroxylation of biphenylin vitro by liver preparations of various species. Biochem. J., 96: 879–885.
Daniel, J.W., James, G.W.L., Rowlands, D.A. and Taylor, J.B. 1978. The physiological dispostion of the antitussive agent, 1,2,3,4,4a,9b-hexahydro-8,9b-dimethyl-4(3-(4-methylpiperazin-1-yl)propionamido)dibenzofuran-3-ont dihydrochloride, azipranone, in man, rat, dog and baboon. Xenobiotica 8: 321–329.
Guengerich, F.P. 1979. Isolation and purification of cytochrome P-450 and the existence of multiple forms. Pharmac. Therap., 6: 99–121.
Hlavica, P. and Hulsmann, S. 1979. Studies on the mechanism of hepatic microsomal N-oxide formation. N-Oxidation of N,N-dimethylaniline by a reconstituted rabbit liver microsomal cytochrome P-448 enzyme system. Biochem. J., 182: 109–116.
Ioannides, C., Delaforge, M. and Parke, D.V. 1981a. Safrole: Its metabolism, carcinogenicity and interactions with cytochrome P-450. Food & Chem. Toxicol., 19: 657–666.
Ioannides, C., Parkinson, C. and Parke, D.V. 1981b. Activation of benzo(a)pyrene and 2-acetamidofluorene to mutagens by microsomal preparations from different animal species: Role of cytochrome P-450 and P-448. Xenobiotica, 11: 701–708.
Joint Meeting of FAO and WHO on Pesticide Residues, Report 1980. 1981. FAO Plant Production and Protection Paper 26, pp.6–7; 53–56, FAO, Rome.
Longmuir, I.S., Gottlieb, S.F., Pashko, L.L. and Martin, P. 1980.In vivo andin vitro induction of cytochrome P-450 synthesis in hyperoxia. Undersea Biomed. Res., 7: 161–170.
Mitchell, J.R., Jollow, D.J., Potter, W.Z.,etal, 1973. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J. Pharmac. exp. Therap., 187: 185–194.
Pacifici, G.M., Boobis, A.R., Brodie, M.J., McManus, M.E. and Davies, D.S. 1981. Tissue and species differences in enzymes of epoxide metabolism. Xenobiotica 11: 73–79.
Parke, D.V. and Ioannides, C. 1982. Role of mixed-function oxidases in the formation of biological reactive intermediates. In: Biological Reactive Intermediates. II. Chemical Mechanisms and Biological Effects, edited by R. Snyder, D.J. Jollow, D.V. Parke, G.G. Gibson, J.J. Kocsis, & C.M. Wither, in press, Plenum, New York.
Phillipson, C.E., Ioannides, C., Delaforge, M. and Parke, D.V. 1982. Studies on the substrate binding sites of liver microsomal cytochrome P-448. Xenobiotica, in press.
Pohl, L.R., Branchflower, R.V., Highet, R.J., Martin, J.L., Nunn, D.S., Monks, T.J., George, J.W. and Hinson, J.A. 1981. The formation of diglutathionyl dithiocarbonate as a metabolite of chloroform, bromotrichloromethane, and carbon tetrachloride. Drug Metabolism Disposition, 9: 334–339.
Schenkman, J.B., Greim, H., Zange, M. and Remmer, H. 1969. On the problem of possible other forms of cytochrome P-450 in the liver microsomes. Biochim. Biophys. Acta, 171: 23–31.
Tanayama, S. 1973. Metabolism of 6-chloro-5-cyclohexindane-1-carboxylic acid (TAI-284), a new non-steroidal anti-inflammatory agent. III. Species differences in metabolism. Xenobiotica, 3: 671–680.
Walker, C.H. 1978. Species differences in microsomal mono-oxygenase activity and their relationship to biological half-lives. Drug Metabolism Rev., 7: 295–323.
Walker, C.H. 1980. Species variations in some hepatic microsomal enzymes that metabolize xenobiotics. In: Progress in Drug Metabolism, Vol.5, pp. 113–164, edited by J.W. Bridges and L.F. Chasseaud, Wiley, London.
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Parke, D.V. Species differences in pharmacokinetics. Vet Res Commun 7, 285–300 (1983). https://doi.org/10.1007/BF02228636
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DOI: https://doi.org/10.1007/BF02228636