Leucovorin Calcium Powder CAS 1492-18-8

Folinic acid calcium salt is a formylated derivative of reduced folic acid, which is similar to folic acid and is an activated form of folic acid in the body. After entering the human body, it is converted into tetrahydrofolate by tetrahydrofolate reductase, which can effectively resist the toxic reaction caused by methotrexate. Therefore, in clinic, calcium folinate powder is often used as an antidote for folic acid antagonists, while high-quality Leucovorin Calcium powder is yellowish white to yellow crystalline or amorphous powder which is easily soluble in water at room temperature.

What are the pharmacological effects of Leucovorin Calcium?

As a highly effective biochemical regulator, calcium folinate (CF) has no anti-tumor effect. It is mainly used in high-dose rescue and in combination with fluorouracil to strengthen the therapeutic effect of the latter, so as to deal with the treatment of gastrointestinal tumors, breast cancer, head and neck cancer, trophoblastic tumors and other malignant tumors. In addition, Leucovorin Calcium powder is a calcium salt of the formyl derivative of calcium tetrahydrofolate, which is the activated form of folate in the body. Competitive inhibition of dihydrofolate reductase prevents folate from transforming into tetrahydrofolate, leading to DNA synthesis disorders. Supplementing with calcium formyl tetrahydrofolate can have a detoxifying effect. And it can treat megaloblastic anemia caused by folate deficiency, promote the differentiation, maturation, and release of bone marrow hematopoietic cells. Clinical studies have found that calcium folinate, as a highly efficient biochemical regulator and fluorouracil based pyrimidine antagonist, can significantly enhance the anti-tumor activity of fluorouracil (5-FU) drugs.

What is the clinical application principle of the combination of calcium folinate and fluorouracil?

The combination of calcium folinate and fluorouracil to enhance the efficacy of the latter is generally referred to as the CF-FU combination therapy. It is currently the first backup plan for the treatment of colorectal cancer in clinical practice. The principle of its treatment plan is that deoxyuridine (dUMP) needs to undergo methylation from tetrahydrofolate (THF) under the catalysis of adenosine monophosphate synthase (TMPS) during DNA synthesis to form deoxyadenosine monophosphate (dTMP). At this point, dihydrofolate reductase converts dihydrofolate into tetrahydrofolate. The main mechanism of action of fluorouracil is to convert it into fluorouracil deoxyribonucleotides after entering the human body, inhibiting TMPS. During the reaction process, TMPS, THF, and dUMP3 form a transitional complex. After the general reaction is completed, this complex decomposes, releasing dihydrofolate, TMPS, and dTMP. But after giving FU, this complex cannot be decomposed, the function of the enzyme is inhibited, and dTMP cannot be generated. The binding affinity between fluorouracil deoxyribonucleotides and enzymes is proportional to the concentration of THF. Increasing the supply of THF can enhance the inhibitory effect of FU on TMPS.

What are the differences between calcium folinate and calcium levofolinate?

Leucovorin Calcium powder is an N5 formyl derivative of tetrahydrofolate, which is a racemic mixture of diastereomers. It can be demethylated under the action of vitamin B12 to form tetrahydrofolate, which is then converted to N-formyl tetrahydrofolate under the action of serine hydroxymethyltransferase. Tetrahydrofolate is closely related to the synthesis of purines and pyrimidines, as well as the metabolism of amino acids. Calcium levofolinate powder is the left-handed form of calcium folinate and also the pharmacological active ingredient of calcium folinate in the body. When used in combination with chemotherapy drugs, Calcium levofolinate only requires half the dose to produce similar therapeutic effects as calcium folinate.

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