Abstract:
Antifolate drugs such as methotrexate, aminopterin, pyrimethamine and trimethoprim have a wide clinical application in the treatment of a number of diseases. Folate antagonists such as methotrexate (MTX) and aminopterin have been commonly used in the prophylaxis and treatment of various leukemias and avariety of neoplasms, whereas, pyrimethamine is an antimalarial drug which is also used in treating toxoplasmosis. The frequent use of these drugs in therapy is generally associated with toxic side effects. For example, intrathecal administration of MTX in the treatment of leukemia and neoplasms metastatic to central nervous system often results in neurological complications. Furthermore, MTX when given systemically also lead to hepatotoxicity and severe myelosuppression. On the other hand, pyrimethamine in large doses, cause megaloblastic anemia. Therapeutic management of these drugs has lad to the development of several assay procedures. By measuring the competition of these drugs against [3H] MTX for the binding sites on partially pure goat liver dihydrofolate reductase, we have devised a simple assay procedure for the measurement of these antifolate agents. Sensitivity of detection of methotrexate, and aminopterin is in the picogram range, while that of pyrimethamine and trimethoprim is in the range of nanograms and micrograms, respectively. The procedure is simple, reliable, rapid, reproducible and is routinely used in our biochemistry laboratory.
Page(s):
11-23
DOI:
DOI not available
Published:
Journal: Pakistan Journal of Pharmacology, Volume: 5, Issue: 2, Year: 1988