The general subject matter of the present article has been considered in previous reviews under the title of "Detoxication Mechanisms." The term "detoxication" was originally employed on the assumption that the metabolism of a drug or toxic substance followed special pathways and proceeded in the direction of the formation of less toxic compounds (1). In 1941 Stekol (2) pointed out that such an assumption was unwarranted in view of the lack of information concerning the relative toxicities of parent sub stances and their derivatives and in view of the findings that the metabolic mechanisms were usually no different from those opera ting in the normal transformation of food stuffs. Handler & Perlzweig (3) and Welch & Bueding (4) re-emphasized this ap proach and cited instances in which the conversion products had been revealed to be more toxic than the parent substances. It has also been shown that some substances do not exert their charac teristic toxic or pharmacological activities until they have under gone a metabolic change.There is still another way in which the term "detoxication" has proven inappropriate. The literature reveals an increasing preoccupation with the metabolism of drugs or substances which are of therapeutic importance. This seems quite fitting, for there is no essential difference in this· respect between drugs and toxic substances. Drugs in doses greater than those employed for thera peutic effects become toxic substances and, similarly, compounds usually considered as toxic have at times been employed in smaller doses for therapeutic purposes. In view of these considerations, we shall, as the title of our review indicates, concern ourselves with the metabolism of drugs and toxic substances with attention to but without bias regarding the relative toxicity or pharmacological effectiveness of the original and derived substances. The subject may be approached either from the viewpoint of a chemical or pharmacological classification 303 Annu. Rev. Biochem. 1948.17:303-326. Downloaded from www.annualreviews.org Access provided by University of California -Davis on 02/05/15. For personal use only. Quick links to online content Further ANNUAL REVIEWS