Effect of trimethoprim on folate-dependent DNA synthesis in human bone marrow

The effect of trimethoprim in various concentrations was tested on the folate-dependent deoxyuridylate methylation reaction in human bone marrow cultures. A slight effect was demonstrated at a concentration similar to that achieved in the plasma in patients taking the conventional therapeutic dose of trimethoprim. When a tenfold greater concentration was used, the effect became more pronounced. These findings are in agreement with reports of some mild haematological changes associated with the use of trimethoprim and offer an explanation for such changes.