Clinical Chemistry, Vol 26, 1617-1619, Copyright © 1980 by American Association for Clinical Chemistry

Trimethoprim interferes with serum methotrexate assay by the competitive protein binding technique

K Hande, J Gober and R Fletcher

Administration of Bactrim (a combination of trimethoprim and sulfamethoxazole) to a patient who also was receiving methotrexate caused a significant increase in apparent plasma methotrexate concentrations as determined by competitive protein binding assay with use of dihydrofolate reductase (EC 1.5.1.3) from Lactobacillus casei as the binding protein. This spurious increase was caused by trimethoprim in the patient's plasma. A plasma trimethoprim concentration of 0.1 mg/L inhibited binding of radiolabeled methotrexate to dihydrofolate reductase by 50%. In contrast, radioimmunoassay for methotrexate was not affected by concomitant administration of trimethoprim. The competitive protein binding assay for methotrexate should not be used in patients being treated with Bactrim or Septra (a similar combination). However, the L. casei competitive protein binding assay technique can be used to assay plasma trimethoprim concentrations with sensitivity to 0.02 mg of trimethoprim per liter.

The following articles in journals at HighWire Press have cited this article:

				B. C. Widemann, F. M. Balis, and P. C. Adamson Dihydrofolate Reductase Enzyme Inhibition Assay for Plasma Methotrexate Determination Using a 96-Well Microplate Reader Clin. Chem., February 1, 1999; 45(2): 223 - 228. [Abstract] [Full Text] [PDF]

				J. A. STOCKMAN III Trimethoprim-Sulfamethoxazole Therapy: Everything's Not Turning up Roses Arch Pediatr Adolesc Med, December 1, 1981; 135(12): 1094 - 1095. [Abstract] [PDF]