Calcium folinate

Mechanism of action and metabolism

In the human body, folic acid is not synthesized de novo (unlike bacteria, which form it from para-aminobenzoic acid). Humans obtain it enterally (from plant and animal foods) or through synthesis by the gut microflora.

The vitamin itself is inactive. In the liver, it undergoes bioactivation, turning into tetrahydrofolic acid (THFA). This process is a cycle:

1. Dihydrofolic acid is reduced to THFA.
2. The reaction is catalyzed by the enzyme dihydrofolate reductase (DHFR).
3. THFA acts as a coenzyme — a donor of single-carbon groups (methyl and formyl).
4. Having donated the carbon, THFA is oxidized back to dihydrofolic acid, and the cycle repeats.

Calcium folinate (Calcium folinate) is essentially the ready-to-use active form (a derivative of THFA). It immediately enters biochemical processes, ensuring the synthesis of DNA and RNA precursors (purine nucleotides, thymidylate), as well as amino acid metabolism (methionine, serine, glycine).

Pharmacological effects

The main pharmacological effect of the drug is antianemic.

By providing cells with building blocks for nucleic acids, the drug:

• Supports normal proliferation (division) of rapidly renewing cells.
• Stimulates erythropoiesis by regulating the proper maturation of megaloblasts and their transition into normoblasts.
• Improves iron absorption in the gastrointestinal tract.

Indications for use

The drug is prescribed for conditions associated with folate deficiency or blocked folate metabolism:

• Antidote therapy: elimination of the toxic effects of folic acid antagonist drugs (methotrexate, trimethoprim, triamterene, pyrimethamine). These drugs block DHFR, and calcium folinate bypasses this block.
• Hematology: macrocytic hyperchromic anemia, leukopenia, and other types of anemia.
• Combination therapy: oncological, neurological, and gastroenterological diseases (including malabsorption syndrome).
• Phthisiology: reduction of toxicity during tuberculosis treatment.
• Prevention: congenital and acquired hyperhomocysteinemia, as well as conditions with increased folate demand (pregnancy).

Side effects and strict limitations

Allergic reactions are possible during use.

Critical rule: in the treatment of pernicious ($B_{12}$-deficient) anemia, folic acid preparations must be prescribed only together with cyanocobalamin (vitamin $B_{12}$).

Isolated use (monotherapy) with folates in pernicious anemia is unacceptable. The drug rapidly normalizes hematological parameters (blood picture) but does not eliminate neurological symptoms at all. Moreover, against the background of such a "false improvement," neurological disorders can covertly progress.

Administration guidelines and prescription

According to the reference guide, Calcium folinate is available in ampoules as a 0.25% solution in 1 ml and 10 ml. The standard daily dose is 0.005 g (5 mg). It is administered intramuscularly or intravenously.

Calculation: a 0.25% solution contains 0.25 g of the substance in 100 ml, which is 2.5 mg in 1 ml. To administer 0.005 g (5 mg), you will need 2 ml of such a solution.

Prescription example (intramuscularly, 1 ml ampoules): ```latin Rp.: Sol. Calcii folinatis 0.25% - 1 ml D.t.d. N. 10 in ampull. S. Intramuscularly, 2 ml (0.005 g) once daily. ```

Class and exam questions

What else to study on this topic

• Mechanism of action of sulfonamides as competitive antagonists of PABA.
• Pharmacodynamics of methotrexate and trimethoprim (inhibition of dihydrofolate reductase).
• Pathogenesis of funicular myelosis in B12-deficiency anemia.
• Biochemical cycle of purine and pyrimidine base synthesis.
• The role of folic acid in homocysteine metabolism and methionine synthesis.

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