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Effects of Folic Acid and Folinic Acid on Pyrimethamine Teratogenesis in Rats
Authors:Gen KUDO  Eiichi KOKUE  Toyoaki HAYAMA
Affiliation:Laboratory of Veterinary Pharmacology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Saiwai-cho 3–5-8, Fuchu-shi, Tokyo 183, Japan
Abstract:ABSTRACT  The effects of folic acid (FA) and folinic acid (FNA) on the tera-togenicity of the antifolate drug pyrimethamine (PYR) were examined in rats. PYR and FA were orally administered with mashed feed. FNA was intraperitoneal-ly injected. The drugs were administered for 5 days of day 11–15 of gestation. Six groups were made; G-I PYR 1.6 (mg/kg/day), G-II PYR 3.6, G-HI PYR 1.6 + FA 50, G-IV PYR 3.6 + FNA 12, G-V FA 50, G-VI control. No malformations were found in G-I, IV, V and VI. All fetuses in G-II and HI had malformations. Main malformations in G-II and III were cleft palate and brachygnathia. Accordingly it might be demonstrated that the teratogenicity of PYR was potentiated by concurrent FA in rats.
Keywords:pyrimethamine    folic acid    folinic acid    teratogenicity    rat
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