Add time:09/29/2019         Source:infona.pl

Purpose: To detect possible interactions between ()-formyl-tetrahydrofolic acid (leucovorin, ()-fTHF) and (+)-formyl-tetrahydrofolic acid ((+)-fTHF) on the plasma and intracellular pharmacokinetics following their simultaneous administration. Methods: Plasma levels of ()-fTHF, ()-methyl-THF, and (+)-fTHF were determined in samples from four volunteers following the administration of both ()-fTHF and ()-fTHF and in seven patients during a 5-fluorouracil (5-FU)/fTHF combination chemotherapy. In addition, the intracellular uptake of 14C-()-mTHF in the presence of (+)-mTHF at increasing concentrations was measured in vitro. Analyses were performed using a highly specific high-performance liquid chromatography procedure. Results: The pharmacokinetic parameters obtained for ()-fTHF following the administration of ()-fTHF only were: terminal half-life, 1.2h; area under the curve, 10gh/ml; maximum concentration, 12g/ml; clearance, 305ml/min; volume of distribution, 19l. The parameters did not differ significantly as compared with those obtained following the administration of ()-fTHF to both volunteers and patients. There were no differences in the pharmacokinetics of ()-mTHF or in the protein binding of both substances with the different forms of administration. The intracellular uptake of 14C-()-mTHF did not depend on the presence of (+)-mTHF at either concentration. Conclusions: These data suggest that ()-fTHF is not therapeutically superior to ()-fTHF and that the latter is appropriate during combination chemotherapy with 5-FU/fTHF in patients with colorectal cancers.

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