Calcium Levofolinate: A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Calcium levofolinate is a critical adjuvant medication in modern oncology and hematology, representing the pharmacologically active levo-isomer of folinic acid. Unlike its racemic counterpart, leucovorin, which contains an equal mixture of the active levo-isomer and an inactive dextro-isomer, calcium levofolinate delivers a purified, potent form of the drug. This monograph provides a comprehensive analysis of its chemical properties, dual mechanisms of action, pharmacokinetics, clinical applications, and safety profile.

Pharmacodynamically, calcium levofolinate serves two distinct and vital roles. First, as a cytoprotective agent, it provides a reduced folate source that bypasses the enzymatic block induced by folic acid antagonists like high-dose methotrexate. This "rescue" mechanism selectively protects healthy cells from toxicity, enabling the use of more aggressive and effective chemotherapy regimens. Second, it acts as a synergistic potentiator of fluoropyrimidine-based chemotherapy, most notably 5-fluorouracil (5-FU). By forming a stable ternary complex with the enzyme thymidylate synthase and the active metabolite of 5-FU, it prolongs the inhibition of DNA synthesis in cancer cells, thereby enhancing the drug's cytotoxic efficacy. This dual functionality has established it as a cornerstone of treatment for osteosarcoma and as a gold standard in combination regimens for metastatic colorectal cancer.

The pharmacokinetic profile of calcium levofolinate is characterized by rapid conversion to its primary active metabolite, 5-methyltetrahydrofolate (5-MTHF). While parenteral administration ensures complete bioavailability, oral absorption is saturable, limiting the effectiveness of high oral doses. The drug distributes widely throughout the body, including the central nervous system, and is primarily eliminated via renal excretion.