Disposition of 5-methyltetrahydrohomofolate in mice, dogs, and monkeys.
The pharmacologic disposition of [methyl-14C]5-methyltetrahydrohomofolate (MTHHF) has been studied in mice, dogs, and monkeys after parenteral administration of doses of 150 and 1500 mg/m2. Thin-layer chromatography and high-pressure liquid chromatography were used to separate the parent compound from its products. Following ip injection of MTHHF into mice, serum levels rose to a maximum within 1 hour and decreased with a half-life of about 50 minutes. The liver, kidneys, and small intestine of mice contained concentrations of MTHHF greater than that of serum. For dogs and monkeys given an iv injection of MTHHF, serum levels declined in three phases. The third phase was probably associated primarily with loss of the drug from the liver and intestine, where relatively large amounts were retained. Within 24 hours after administration of MTHHF, the percent recovery in the urine was 69% for mice, 78% for dogs, and 50%--60% for monkeys. For mice and dogs an additional 2%--17% was recovered in the feces within 24 hours. Over a period of 3 days after injection with the high dose in a monkey, 24% of the dose was present in the feces. For all three species, 90%--99% of the radioactivity in the serum, urine, and feces was unchanged MTHHF, indicating that very little metabolism or decomposition had occurred. Less than 0.3% of the dose was recovered from monkeys as radioactive CO2.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004285:Dogs; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D000882:Haplorhini; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D013045:Species Specificity; D014018:Tissue Distribution
D001798:Blood Proteins; C020410:5-methyltetrahydrohomofolic acid; D005492:Folic Acid