Antibiotics alter methotrexate metabolism and excretion

Abstract

The chemotherapeutic agent methotrexate is metabolized by the intestinal flora of normal mice. This metabolism is reduced either by treatment of mice with the antibiotics neomycin and sulfathiazole, or in germ-free mice. In addition to affecting metabolism, these antibiotics alter physiological distribution of methotrexate so that excretion by the intestinal route is significantly enhanced.