Effects of Pyrimethamine and Folic Acid on Plasma Level of 5‐Methyltetrahydrofolic Acid in Rats

Publisher Website
Google Scholar
Abstract
The relationship between pyrimethamine (PYR) teratogenesis and the plasma level of 5‐methyltetrahydrofolic acid (5MF), known as an active form of folate in plasma, was studied in rats using an HPLC‐ECD method for 5MF determination. The rat received, for 5 days, in‐feed PYR with or without folic acid (FA), which was previously reported as a potentiator of PYR teratogenesis. PYR alone caused a dose‐dependent decrease in the plasma 5MF level after the 5 day dosings. A potentiated decrease in the 5MF level was observed after the concomitant dosing of PYR with FA. The concomitant dosing of PYR 1.6 mg/kgBW/day (subteratogenic dose of PYR alone) with FA 50 mg/kg/day, which was 100% teratogenic dose in our previous report, decreased the 5MF level more than that after the dosing of PYR 3.6 mg/kg/day alone (100% teratogenic dose of PYR alone).The sequential changes of the plasma 5MF level after the single oral dosing of PYR 3.6 mg/kg with or without oral FA 50 mg/kg also revealed a strong potentiative effect of oral FA on the 5MF‐level‐lowering effect of PYR. These results indicate that a decrease in the plasma 5MF level may be related to PYR teratogenesis.