Trimethoprim and Sulphamethoxazole Inhibition of Haematopoiesis in Vitro

Abstract

The effect of trimethoprim and sulfamethoxazole on hematopoiesis was studied in vitro using cloning techniques for human and murine erythroid and granulocytic precursor cells. Trimethoprim inhibited granulopoiesis and erythropoiesis in vitro in a dose-dependent fashio with approximately 50% inhibition of human erythroid and granulocytic colonies at a therapeutically achievable concentration of 7 .mu.g/ml. Sulfamethoxazole impaired hematopoiesis in vitro. The inhibition caused by both these constituents of co-trimoxazole was completely reversed by folinic acid. Co-trimoxazole can impair human hematopoiesis by inhibition of tetrahydrofolate synthesis. The clinical hematopoietic toxicity of trimethoprim-sulfamethoxazole can apparently be abrogated by simultaneous administration of folinic acid.