Eino Nelson

Part XVII. Physicochemical and pharmaceutic properties of drugs that influence the results of clinical trials

Despite the fact that pharmacologists and some clinicians are aware that physical, chemical, and pharmaceutic properties of a drug may influence its actions and effects, little consideration has been given to quantitating the effects of these properties. It is the aim of this article to discuss and illustrate the fact that the rate of gastrointestinal absorption of a drug is often a function of the time needed for the drug to dissolve in the fluid at the site of absorption. Clinical trials of several forms of the same drug may merely confirm a result which should have been predicted on the basis of its properties, such as specific surface area, type of salt, and the form in which it is administered.

Kinetics of the excretion of sulfonamides during therapeutic dosage regimens

Abstract The relationship between excretion rate of free and acetylated sulfonamides during therapy with this class of drugs was examined with respect to the usual dosage regimen employed, the kinetics of their absorption and metabolism, and with respect to the volumes of urine needed to be secreted to prevent crystalluria. The equations developed allow the calculation of the excretion rate of unchanged and acetylated sulfonamides at times of dosage and in the interval between doses. Using sulfathiazole, as an example, it was found that excretion rate of acetylsulfathiazole after administration of a sufficient number of doses to yield constant values for excretion rate of this material at times of dosage, was relatively independent of drug absorption rate. Similarly, excretion rate between doses was relatively independent of drug absorption rate and did not deviate too markedly from the rate at times of dosage. On the basis of these calculations, high rates of urine flow need to be maintained in order to prevent crystalluria. Calculations on excretion rate of unchanged sulfathiazole indicated that crystalluria due to this material is possible.