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Content:
Chapter 1 Chairman's creation (pages 1–2):
Chapter 2 The function of the Drug?Metabolizing Enzymes (pages 5–24): James W. Bridges
Chapter three The impression of Inducers on Drug?Metabolizing Enzyme job and on Formation of Reactive Drug Metabolites within the Liver (pages 25–42): Sten Orrenius, Hjordis Thor and Bengt Jernstrom
Chapter four results of Inducers and Inhibitors on Drug?Metabolizing Enzymes and on Drug Toxicity in Extrahepatic Tissues (pages 43–66): Michael R. Boyd
Chapter five Induction of Enzymes excited by DNA fix and Mutagenesis (pages 67–81): B. A. Bridges
Chapter 6 Induction of Drug?Metabolizing Enzymes by means of Polycyclic fragrant Hydrocarbons: Mechanisms, and a few Implications in Environmental well-being examine (pages 83–99): John R. Bend
Chapter 7 Induction of Drug?Metabolizing Enzymes by means of Phenobarbitone: Structural and Biochemical points (pages 101–118): Urs A. Meyer, Peter J. Meier, Hans Hirsiger, Urs Giger and Felix R. Althaus
Chapter eight Substrate?Dependent Irreversible Inactivation of Cytochrome P?450: Conversion of Its Haem Moiety into transformed Porphyrins (pages 119–139): Francesco De Matteis, Anthony H. Gibbs, Lavinia Cantoni and Jean Francis
Chapter nine legislation of Human Drug Metabolism by way of nutritional elements (pages 147–167): A.H. Conney, M.K. Buening, E.J. Pantuck, C.B. Pantuck, J.G. Fortner, K.E. Anderson and A. Kappas
Chapter 10 Infiuence of international Compounds on Formation and Disposition of Reactive Metabolites (pages 169–189): F. Oesch
Chapter eleven Pharmacokinetic elements Governing the Steady?State Concentrations of international chemical substances and Their Metabolites (pages 191–217): James R. Gillette
Chapter 12 Toxicological Implications of Polymorphic Drug Metabolism (pages 219–244): J.C. Ritchie, T.P. Sloan, J.R. Idle and R.L. Smith
Chapter thirteen Immunologically Mediated Toxicity (pages 245–259): H.E. Amos
Chapter 14 Toxicological importance of Liver Hypertrophy Produced via Inducers of Drug?Metabolizing Enzymes (pages 261–274): Emmanuel Farber
Chapter 15 The effect of food and Inducers on Mechanisms of Toxicity in people and Animals (pages 275–288): Andre E.M. McLean, David J. Wltts and Denise Tame
Chapter sixteen effect of Environmental chemical substances on Drug remedy in people: reports with Contraceptive Steroids (pages 289–306): A.M. Breckenridge, D.J. again, Karen pass, Francesca Crawford, M. MacIver, M. L'E Orme, P.H. Rowe and Eileen Smith
Chapter 17 nutrition D Metabolism in sufferers taken care of with Phenytoin and Phenobarbitone (pages 315–330): J.O. Hunter and M. Davie
Chapter 18 Chemical illness in people: difficulties in Comparative Toxicology (pages 331–347): Irving J. Selikoff
Chapter 19 Implications for destiny experiences in people (pages 349–358): John Higginson

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Sample text

PREDICTIONS OF EFFECTS OF‘ INHIBITORS AND INDUCERS OF DRUG-METABOLIZING ENZYMES ON EXTRAHEPATIC DRUG METABOLISM AND TOXICITY In assessing the effects of pretreatment with a particular drug upon the metabolism and toxicity of another foreign compound, we must take into account the time course of administration of the pretreatment. When administered chronically, many ‘inhibitors’ of drug-metabolizing enzymes may act as inducers. Similarly, drugs which typically are viewed as ‘inducers’ may act as inhibitors if they are present in sufficiently high concentrations in the tissues at the time of administration of the toxic compound.

1, the parent compound alone is the ultimate toxic agent responsible for damage to extrahepatic tissue in mechanism ‘A’. The extrahepatic organ in which toxicity develops may depend upon selective exposure, preferential uptake or preferential concentration of the toxic agent in the target tissue, or upon the presence of specific receptors or other highly susceptible sites of action. Alternatively, there may be little selectivity of target organ; the toxic agent may affect the liver as well as many extrahepatic sites.

It stimulates the phase I1 reactions in preference to the P-450 reactions. This type of inducer could therefore be quite significant in reducing toxicity. Gillette: We need to be cautious though, because there can be a species difference in inducibility. For example, the paracetamol toxicity is decreased in hamsters but increased in mice by pretreatment with phenobarbitone (Potter et a1 1974, Mitchell et a1 1973). Cancer Res 39:2971-2977 Cha Y N , Bueding E 1979 Effect of 2(3)-tert-butyl-4-hydroxyanisoleadministration on the activities of several hepatic microsomal and cytoplasmic enzymes in mice.

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