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Schalhorn, A.* ; Siegert, W.* ; Sauer, H.J.

Antifolate effect of triamterene on human leucocytes and on a human lymphoma cell line.

Eur. J. Clin. Pharmacol. 20, 219-224 (1981)

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The inhibitory effect of triamterene and its metabolites on human leucocyte dihydrofolate reductase has been studied. Under test conditions with dihydrofolic acid 0.5×10-5 M, triamterene 7×10-5 M produced total enzyme inhibition, whereas the metabolites hydroxytriamterene and the sulphate ester of hydroxytriamterene were less effective inhibitors; at their maximum attainable concentration of 5×10-5 M, dihydrofolate reductase was inhibited by 80% and 50%, respectively. Cultures of the BJAB-B95-8 human lymphoma cell line were incubated with various concentrations of triamterene. Because of their increased specific activity of dihydrofolate reductase, the cells were able to maintain normal DNA metabolism, as measured by the ratio of the incorporation rates of 3H-deoxyuridine and 3H-thymidine, as well as normal cell growth at 1×10-6 M, and in some cases at 1 × 10-5 M triamterene. At 8×10-5 M triamterene, the strong inhibitory effect caused severe impairment of DNA metabolism and subsequently dissolution of the cell culture. The results are discussed in relation to the possible toxic side effects of long-term triamterene treatment in patients suffering from alcoholic cirrhosis, who may have impaired metabolism of triamterene and a concomitant severe folate deficiency.

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