Measurement of Antifolate Drugs by Microbiological Assay.

摘要

A detailed description of the methods used to calculate the plasma levels of an antifolate compound from data obtained with the Streptococcus faecium assay is presented. Compounds which compete with folic acid (folic acid antagonists, FAAs) become limited in their usefulness in the treatment of leukemia, malaria and bacterial infections by the rapid development of resistance. Assays of the plasma levels of certain of these FAAs led to the observation, in about 25% of the determinations, that a higher density of growth of Streptococcus faecium var. durans (ATCC 8043) was obtained at an FAA concentration just below the completely inhibitory level than at one-half this concentration. Seven FAAs including amethopterin, pyrimethamine, trimethoprim, chlorguanide triazine, an experimental quinazoline, WR-158,122, and two experimental triazines, WR-99,210 and WR-38,839, were tested for mutagenicity in the Salmonella reversion assay developed by Ames. All were found to be negative for negative for strains TA1535, TA1537, TA98 and TA100, both with and without microsomal activation.