@article{3136139, title = "The effect of trimethoprim and sulphamethoxazole on human dihydrofolate reductase", author = "Tzortzatou-Stathopoulou, F. and Thomaidis, T.H. and Manolaki, N. and Bibou-Koutsoukou, A. and Matsaniotis, N.", journal = "Pediatric Hematology and Oncology", year = "1984", volume = "1", number = "1", pages = "67-70", publisher = "LIBRAPHARM/INFORMA HEALTHCARE", issn = "0888-0018, 1521-0669", doi = "10.3109/08880018409141711", keywords = "antiinfective agent; cotrimoxazole; dihydrofolate reductase; enzyme; sulfamethoxazole; trimethoprim, blood and hemopoietic system; drug efficacy; etiology; folate metabolism; human; human cell; human experiment; methodology; normal human; oral drug administration; therapy", abstract = "The effect of trimethoprim and sulphamethoxazole on human dihydrofolate reductase was studied in vivo using cytochemical methods applied prior, during and after trimethoprim and sulphamethoxazole treatment in 36 children (3 months-14 years). The doses used were 4-7 mg/kg/day of trimethoprim and 20-35 mg/kg of sulphamethoxazole up to maximal duration of 1 year. Although 15 children showed decreased enzyme activity during treatment with trimethoprim and sulphamethoxazole, red and white cell morphology was nevertheless normal. Six of these children had reduced enzyme activity over 4 months and they did not develop megaloblastic abnormalities. Treatment was not discontinued and folates were not added. Enzyme activity returned to normal after drug administration was discontinued. The other 21 children did not show decreased enzyme activity. With the above simple method, it is easy to reveal early effects of trimethoprim and sulphamethoxazole on folate metabolism. This study also indicates that prophylactic folate co-administration is not necessary. © 1984 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted." }