The fate of acetanilide in man.

Therapeutic agents, in general, undergo chemical alteration in the body to form derivatives of the parent compound. Isolation and pharmacological assay of the various transformation products may yield valuable information in the Senrch for better therapeutic agents, in studies on the mechanism of drug action :,*d in the elucidation of norm+l metabolic processes. The therapeutic effect of a drug could be limited by a chemical change which results in a less active or an inactive product. Knowledge of the nature of this metabolic product may suggest the introduction of substituents in the parent drug that would prevent the transformation and thereby enhance its activity. On the other hand, it is possible that the parent drug itself is inert but produces :I therapeutic effect incidental to the formation of a highly active metabolic product. Knowledge of the structure of this derived product may suggest a synthesis of more effective derivatives. Again, the toxicity of the drug could reside in a derived product the formation of which, if its structure be known, may be blocked by an appropriate modification of the parent drug. Fundamental studies on the mechanism of drug action attempt to correlate the effect of a drug on ensymatic activity with its pharmacological activity. The compound possessing the pharmacological action may be a product derived in the body from the parent drug. It is obvious in this case that the studies should be made not with the parent drug but with the active derived product. It is unlikely that special ensymes exist in the body for the chemical transformation of each drug. Rather, it is likely that a drug undergoes chemical change by becoming involved in biochemical reactions whic,h ordinarily handle normally occurring substances. The presence of a particular ensyme system within the animal is indicated by the transform&on of’ the foreign compound. Knox used the transformation of quinine to 2-hydroxy quinine by various tissues as an indicator in the isolation in-relatively pure form of the so-called quinine oxidase. He found this enzyme normally to be involved in the metabolism of nicotinamide (1). The study of drugs fr,om the above points of view has been considerably facilitated by two recent developm&ts: .I, a scheme whereby simple and sensitive analytical methods for nitrogenous bases in biological material may readily be devised; included in thii scheme is a technique for identifying the substance measured by means of its solubility &aracteristics (2, 3) ; 2. the technique of counter-current distribution which has been applied to the fractionation and isolation of substances from biological material (4).