Disposition of 5-methyltetrahydrohomofolate and methotrexate in rats.

The pharmacologic disposition of [methyl-14C]5-methyltetrahydrohomofolate (MTHHF) and [3H]methotrexate (MTX) has been studied in rats after iv doses of 25 mg/kg. Thin-layer chromatography and high-pressure liquid chromatography were used to separate the parent compounds from possible products. In rat serum, levels of MTHHF decreased with half-lives of 7 and 55 mins; for MTX, the corresponding values of half-lives were 14 and 54 mins. No metabolites of MTHHF or MTX were found in the samples assayed. At 3, 6, and 24 hrs after administration of MTHHF or MTX, liver, kidney, and small intestine contained concentrations of the drugs greater than those in serum. In rats with cannulated bile ducts, 16% of 60% of the doses of MTHHF and MTX, respectively, were excreted in the bile within 4 hrs. In 24 hrs, 51% of the dose of MTHHF and 41% of the dose of MTX were excreted in the urine of rats without bile cannulas. During the same time, fecal excretion accounted for 21% of the dose of MTHHF and 17% of the dose of MTX. The data indicate that enterohepatic circulation is probably extensive for MTX but less so for MTHHF.