Pharmacokinetics of the Diastereoisomers of Leucovorin after Intravenous and Oral Administration to Normal Subjects

摘要: After i.v. administration of d,l-, 1-5-formyltetrahydrofolate (d,l-CHO-THF) CHO-THF was rapidly cleared from the plasma by conversion to 5-methyltetrahydrofolate (5-CH3-THF) and urinary excretion, whereas d-CHO-THF, which not metabolized slowly excreted in urine, persisted at concentrations greatly exceeding those l-CHO-THF 5-CH3-THF. The half-life (beta) unnatural (d) isomer 451 +/- 24 (S.E.) min compared 31.6 1.1 for natural (l) isomer, 227 20 its active metabolite, half-lives volumes distribution each three compounds were independent dose over a range 25 100 mg, indicating that mechanisms distribution, metabolism, excretion are saturable tested. clearance or 5-CH3-THF differed only slightly creatinine clearance, d-CHO-THF one-fifth extensively reabsorbed. Absorption d,l-CHO-THF after p.o. stereoselective absorption l-isomer approximately 5 times d isomer. Thus, resulted more favorable ratio inactive folates plasma. At approached 100% 20% d-CHO-THF. However, saturable, lower percentages both absorbed doses 50 mg.