Rifampin in drug-incorporated diet: effect of duration and temperature of storage. Relevance to drug-susceptibility testing in mice inoculated with M. leprae.

This paper is in two parts. Plasma concentrations of rifampin were assayed at 11 time points in 24 hr in mice fed one of three dosages of rifampin, either by gavage or by dietary incorporation. The drug-mixed diets had been stored for a maximum of 3 weeks at 4 degrees C or at room temperature (30 degrees C-35 degrees C). The peak concentration of rifampin produced by gavage was approximately 11/2 times higher than the maximum plasma concentration of the corresponding dosage in fresh diet. Plasma concentrations decreased with the increasing duration of storage of the drug-mixed diet, irrespective of whether the diet was stored at 4 degrees C or at room temperature. This decrease was less when the diet was stored at 4 degrees C than at room temperature. Drug levels were also assayed in another set of mice selected from ongoing drug-susceptibility experiments; these mice were fed a rifampin-incorporated diet stored at room temperature. The plasma concentrations in these mice, assayed at the time of foot pad harvest, were generally higher than in the 24-hr experiment. The harvest results from these mice were compared with the harvest results from a third set of mice, also from ongoing drug-susceptibility experiments, but fed a rifampin-mixed diet stored at 4 degrees C. Multiplication of Mycobacterium leprae in mouse foot pads was prevented by rifampin mixed in the diet at a dosage of greater than or equal to 0.003%, whether stored at room temperature or at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)