title: Pharmacokinetics of folinic acid and 5-methyltetrahydrofolic metabolite after repeated oral administration of calcium folinate following methotrexate treatment.
abstract: The pharmacokinetic profiles of folinic acid (FA) and its active metabolite, 5-methyltetrahydrofolic acid, were studied after oral administration of decreasing doses of calcium folinate during 37 courses of high and intermediate dose methotrexate treatment in 25 lymphoma patients. FA was administered at a dose of 6 x 50 mg in 15 courses, 6 x 25 mg in seven courses, 6 x 15 mg in 10 courses and 6 x 7.5 mg in 5 courses. FA, 5-methyltetrahydrofolic acid, methotrexate and 70H-methotrexate were assayed simultaneously by high performance liquid chromatography. When FA was administered at doses between 50 and 15 mg, maximum concentrations of both the drug and its metabolite were always obtained after 1 to 2 h and remained stable. The same was true for the equilibrium concentration of the two products at doses over 15 mg. These findings suggest saturation of absorption and metabolism of folinic acid at doses over 15 mg.
authors.affiliation: Service d'Oncologie et de Ratiothérapie, CHU Timone, Marseilles, France.
authors.forename: N
authors.initials: N
authors.lastname: Tubiana-Mathieu
authors.forename: S
authors.initials: S
authors.lastname: Monjanel-Mouterde
authors.forename: C
authors.initials: C
authors.lastname: Lejeune
authors.forename: B
authors.initials: B
authors.lastname: Payet
authors.forename: J
authors.initials: J
authors.lastname: Catalin
authors.forename: Y
authors.initials: Y
authors.lastname: Carcassonne
authors.forename: J
authors.initials: J
authors.lastname: Cano
mesh_terms: D000284:Administration, Oral; D000328:Adult; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D013763:Tetrahydrofolates / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D013763:Tetrahydrofolates; D002955:Leucovorin; C005984:5-methyltetrahydrofolate; D008727:Methotrexate