Trimethoprim and Sulphamethoxazole Inhibition of Haematopoiesis in Vitro

The effect of trimethoprim and sulphamethoxazole on haematopoiesis was studied in vitro using cloning techniques for human and murine erythroid and granulocytic precursor cells. Trimethoprim was found to inhibit granulopoiesis and erythropoiesis in vitro in a dose-dependent fashion with approximately 50% inhibition of human erythroid and granulocytic colonies at a therapeutically achievable concentration of 7 micrograms/ml. Sulphamethoxazole was also shown to impair haematopoiesis in vitro. The inhibition caused by both these constituents of co-trimoxazole was completely reversed by folinic acid. The data suggest that co-trimoxazole can impair human haematopoiesis by inhibition of tetrahydrofolate synthesis. These observations suggest that the clinical haematopoietic toxicity of trimethoprim-sulphamethoxazole can be abrogated by simultaneous administration of folinic acid.