Inhibition of Drug Metabolism

Abstract

Rates of drug metabolism in animals can be reduced in a variety of ways: adrenalectomy (Remmer, 1958a, b), alloxan induced diabetes (Dixon et al., 1961, 1963), administration of inhibitors of protein synthesis, such as ethionine (Conney et al., 1956, 1960; Fujimoto and Plaa, 1961), actinomycin D (Orrenius and Ernster, 1964; Gelboin and Blackburn, 1964), puromycin (Orrenius and Ernster, 1964; Gelboin and Blackburn, 1964) and thioacetamide (Sladek and Mannering, 1969a). Drug metabolism can also be inhibited by X-irradiation (Varagić et al., 1962; Hietbrink and Dubois, 1964; Dubois, 1967) and alkylating agents which mimic the action of X-irradiation (Tardiff and Dubois, 1969), administration of yellow phosphorus (Herken et al., 1958; Neubert and Maibauer, 1959) or radioactive phosphate (Sulser et al., 1966), starvation (Dixon et al., 1960; Kato and Gillette, 1965), and vitamin C deficiency (Axelrod et al., 1954b; Conney et al., 1961). This chapter is not concerned with these indirect means of depressing drug metabolism; it will restrict itself to inhibition as it is more narrowly denned to mean the interference of the metabolism of one agent by another agent at the enzymic site. This automatically excludes such agents as thyroxin (Cochin and Sokoloff, 1960; Conney and Garren, 1961; Mannering et al., 1969), morphine (Axelrod, 1956a; Mannering and Takemori, 1959; Chaplin et al., 1968), CCl4 (Castro et al., 1968; Dingell and Heimberg, 1968; Sasame et al., 1968), 3-amino-1,2,4-triazole (Kato, 1967; Baron and Tephly, 1969), and p-aminosalicylic acid (Rogers et al., 1963a), which are thought to reduce drug metabolism by mechanisms other than direct inhibition at the metabolic site.KeywordsDrug MetabolismLiver MicrosomeHepatic MicrosomePolycyclic HydrocarbonPiperonyl ButoxideThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.