Pharmacokinetic model for 2-amino-1,3,4-thiadiazole in mouse, dog, and monkey

A mathematic model has been developed to describe the time course of 2-amino-1,3,4-thiadiazole and its metabolites in the serum and tissues of mice, dogs, and monkeys. A flow-limited physiologic model has been used. The rate of metabolism in mice is described as a linear process; metabolism in dogs and monkeys is kinetically saturable. The urinary excretion in mice, dogs, and monkeys is described as a linear process; however, the kidney clearance in monkeys may decrease at high plasma concentrations. The model predictions are compared with published data. The kidney clearances of 2-amino-1,3,4-thiadiazole and its metabolites exhibit approximately a 0.7-power dependence on body weight when the mouse is compared with the larger species.