Comparative Pharmacology
Head-to-head clinical analysis: LEUCOVORIN CALCIUM versus LEUCOVORIN CALCIUM PRESERVATIVE FREE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: LEUCOVORIN CALCIUM versus LEUCOVORIN CALCIUM PRESERVATIVE FREE.
LEUCOVORIN CALCIUM vs LEUCOVORIN CALCIUM PRESERVATIVE FREE
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Leucovorin calcium is a reduced form of folic acid that serves as a cofactor in nucleic acid synthesis. It is converted to tetrahydrofolate (THF), which is essential for purine and pyrimidine biosynthesis. It bypasses dihydrofolate reductase (DHFR), allowing continued DNA synthesis in the presence of methotrexate or other DHFR inhibitors.
Leucovorin is a reduced form of folic acid that bypasses dihydrofolate reductase inhibition, providing a source of tetrahydrofolate for DNA synthesis and repair. It rescues normal cells from methotrexate toxicity by replenishing reduced folate pools.
15 mg orally, intramuscularly, or intravenously every 6 hours for 5 to 7 doses; for rescue after high-dose methotrexate: 10 mg/m2 every 6 hours until serum methotrexate level <5×10^-8 M; for advanced colorectal cancer: 200 mg/m2 IV over 2 hours with 5-fluorouracil 370 mg/m2 IV bolus on days 1-5 every 28 days.
For rescue after high-dose methotrexate: 10 mg/m2 orally, intravenously, or intramuscularly every 6 hours for 10 doses. For advanced colorectal cancer: 200 mg/m2 intravenously over 2 hours daily for 5 days every 3 weeks (with 5-FU).
None Documented
None Documented
Leucovorin (5-formyltetrahydrofolate) has a terminal half-life of approximately 6.2 hours for the active [6S]-isomer and 31-33 hours for the inactive [6R]-isomer. The active metabolite, 5-methyltetrahydrofolate, has a half-life of about 3.5 hours. Clinical context: Half-life is dose-dependent and prolonged in renal impairment.
The terminal elimination half-life of calcium folinate is approximately 6-7 hours. The active metabolite, 5-MTHF, has a terminal half-life of about 11-12 hours. This longer half-life supports prolonged plasma levels required for rescue therapy following high-dose methotrexate.
Primarily excreted in urine as inactive metabolites (80-90%) and unchanged drug (<5%). Fecal excretion accounts for 5-10% via biliary elimination of metabolites.
Renal excretion of calcium folinate (leucovorin) and its active metabolite, 5-methyltetrahydrofolate (5-MTHF), accounts for approximately 80-90% of elimination; fecal excretion is minimal. Approximately 50% of an administered dose is excreted unchanged in urine within 24 hours.
Category C
Category C
Antidote (Folate Analog)
Antidote (Folate Analog)