Effects of Folic Acid and Folinic Acid on Pyrimethamine Teratogenesis in Rats
Gen Kudo, Eiichi KOKUE, Toyoaki HAYAMA
Abstract
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Gen Kudo, Eiichi KOKUE, Toyoaki HAYAMA
Abstract
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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.
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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.
Key concepts: Folinic acid, Pyrimethamine, Folic acid, Teratology, Pharmacology, Antifolate, Chemistry, Medicine