Premium
Effect of Folic Acid on Pharmacokinetics of Pyrimethamine in Rats
Author(s) -
TSUNEMATSU Kunitoshi,
SHIMODA Minora,
HAYAMA Toyoaki
Publication year - 1992
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/j.1741-4520.1992.tb00260.x
Subject(s) - pharmacokinetics , dosing , concomitant , pharmacology , fetus , teratology , chemistry , gestation , medicine , pregnancy , biology , genetics
The effect on pyrimethamine (PYR) pharmacokinetics of folic acid (FA) which potentiated the PYR teratogenesis was studied in rats. Gavage administration of PYR 1.6 mg/kgBW/day from day 11 to day 15 of gestation did not cause any malformation, but with concomitant dosing of FA 50 mg/kg/day in feed caused malformations in 75% of fetuses. Neither the plasma concentration‐time profile nor the plasma protein binding of the gavaged PYR was affected by the concomitant dosing of FA in the non‐pregnant rats. The pregnant rats which received the gavaged PYR with or without FA in feed for 5 days (from day 11 to day 15 of gestation) were killed at 4 or 12 hrs after the last dosing of PYR, and their plasma and fetuses were subjected to determination of PYR. The PYR concentration in the maternal plasma was comparable in both groups. The PYR concentration in fetuses of the PYR alone group was significantly higher than that of the PYR with FA group 4 hr after but not 12 hr after the last dosing. These results indicated that the pharmacokinetics of PYR was not affected by the concomitant dosing of FA, suggesting that FA potentiated the PYR teratogenesis by other mechanisms than pharmacokinetic modifications.