Minimum Rates of Flow in Therapy with Sulphonamides

Abstract

RECENT work on the kinetics of the acetylation of sulphisoxazole¹ and sulphamethylthiadiazole² in human beings indicate that excretion of acetylated drug is the terminal step in a two-step consecutive first-order process the first step of which is acetylation. This kinetic model was tested for ability to describe the metabolism and excretion of sulphathiazole taken by normal adult humans under a standard test procedure¹. When 0.5-gm. doses were taken, excretion of acetylated drug was well described by the appropriate mathematical expression^1,2. However, when one subject took a 1.0-gm. dose, it was not possible to describe the excretion of acetylated sulphathiazole by the same expression. The test was repeated with the same subject about two weeks later, and a water intake of about 500 ml./hr. maintained during the first 8 hr. of the test. This time excretion of the acetylated drug was well described by the expression. Using the rate constants obtained in the second test to calculate maximum excretion-rate of acetylated sulphathiazole by this subject from a 1.0-gm. dose, and comparison of this rate with the average urine flow-rate during the expected time of occurrence of the maximum during the first test, indicated that the solubility of acetylated sulphathiazole was exceeded at the average urine pH. It seemed reasonable to believe that crystalluria had occurred during the first test with a 1.0-gm. dose which would prevent description of excretion by the expression previously found to hold when a smaller dose was taken. There was no evidence of hæmaturia on casual gross examination of the urine specimens obtained in the first test with a 1.0-gm. dose.