Chemical formula: C₂₀H₂₁CaN₇O₇ Molecular mass: 473.446 g/mol PubChem compound: 6006
Calcium folinate (5-formyl tetrahydrofolinate) acts partly by providing a fresh supply of tetrahydrofolate and also by competitively displacing methotrexate from dihydrofolate reductase so that its excretion is accelerated (methotrexate binds to the enzyme dihydrofolate reductase which is responsible for reducing dietary folic acid to dihydrofolate and tetrahydrofolate thus inhibiting its action).
Calcium folinate is the calcium salt of 5-formyl tetrahydrofolic acid. It is an active metabolite of folinic acid and essential coenzyme for nucleic acid synthesis in cytotoxic therapy.
Calcium folinate is frequently used to diminish the toxicity and counteract the action of folate antagonists, such as methotrexate. Calcium folinate and folate antagonists share the same membrane transport carrier and compete for transport into cells, stimulating folate antagonist efflux. Calcium folinate also protects cells from the effects of folate antagonists by repletion of the reduced folate pool. Calcium folinate serves as a pre-reduced source of H4 folate; it can therefore bypass folate antagonist blockage and provide a source for the various coenzyme form as of folic acid.
Calcium folinate is also frequently used in the biochemical modulation of fluoropyridine (5-fluorouracil) to enhance its cytotoxic activity. 5-fluorouracil inhibits thymidylate synthase (TS), a key enzyme involved in pyrimidine biosyntheses, and calcium folinate enhances TS inhibition by increasing the intracellular folate pool, thus stabilising the 5-fluorouracil-TS complex and increasing activity.
Finally intravenous calcium folinate can be administered for the prevention and treatment of folate deficiency when it cannot be prevented or corrected by the oral administration of folic acid. This may be the case during total parenteral nutrition and severe malabsorption disorders. It is also indicated for the treatment of megaloblastic anaemia due to folic acid deficiency, when oral administration is not feasible.
Following intramuscular administration of the aqueous solution, systemic availability is comparable to an intravenous administration. However, lower peak serum levels (Cmax) are achieved.
Following oral administration of a 15mg (7.5mg/m²) dose in healthy men, mean peak serum folate concentrations of 0.268 µg/mL occur within about 1.72 hours. Areas under the serum folate concentration-time curves (AUCs) are reported to be about 8% less following I.M. injection in the gluteal region than in the deltoid region and about 12% less following I.M. injection in the gluteal region than following I.V. or oral administration.
The distribution volume of folinic acid is not known.
Peak serum levels of the parent substance (D/L-formyl-tetrahydrofolic acid, folinic acid) are reached 10 minutes after intravenous administration.
The AUC for L-5-formyl-THF and 5-methyl-THF were 28.4±3.5 mg.min/l and 129±11 mg.min/l, respectively, after a dose of 25mg. The inactive D-isomer is present in higher concentration than L-5-formyl-tetrahydrofolate.
Calcium folinate is a racemate where the L-form (L-formyl-tetrahydrofolate, L-5-formyl-THF), is the active enantiomer.
The major metabolic product of folinic acid is 5-methyl-tetrahydrofolic acid (5-methyl-THF) which is predominantly produced in the liver and intestinal mucosa.
The elimination half-life is 32–35 minutes for the active L-form and 352–485 minutes for the inactive D-form, respectively.
The total half-life of the active metabolites is about 6 hours (after both intravenous and intramuscular administration).
80-90% is excreted in the urine as the inactive metabolites, 5- and 10-formyl-tetrahydrofolate, 5-8% is excreted in the faeces.
None stated.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
