Trimethoprim interferes with serum methotrexate assay by the competitive protein binding technique
Hande, K.; Gober, J.; Fletcher, R.
Clinical Chemistry 26(11): 1617-1619
1980
ISSN/ISBN: 0009-9147 PMID: 6774838 Document Number: 159498
Administration of Bactrim (a combination of trimethoprim and sulfamethoxazole) caused a significant increase in apparent plasma methotrexate concentrations; this was 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 trimethoprim/l.