Pharmacokinetics and bioavailability of folic acid and plasma levels of bioactive folates after folic acid administration to pigs

Abstract

After intravenous (1 mg/kg body weight), intramuscular (1 mg/kg body weight) and oral (1 and 50 mg/kg body weight) administration of folic acid (FA) to pigs, plasma levels of FA, tetrahydrofolic acid (THF), 5-methyltetrahydrofolic acid (5MF) were determined by using high-performance liquid chromatography. The pharmacokinetic profile of plasma FA after oral administration indicated an absorption rate-limited elimination, i.e., so called 'flip-flop' phenomenon. The bioavailability of FA was quite low after a high oral dose (F = 0.01), in contrast to a high value after intramuscular administration (F = 0.95). The plasma levels of biologically active, reduced forms of folates (THF and 5MF) were significantly increased over their basal levels after IV and IM administration to FA. The levels of these active folates were not increased after oral administration of a similar dose of FA. A 50 times higher dose was required to increase the active folates to the levels observed after IV and IM administration.