Comparative Pharmacology
Head-to-head clinical analysis: ADRUCIL versus METHOTREXATE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ADRUCIL versus METHOTREXATE.
ADRUCIL vs METHOTREXATE
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Fluorouracil (5-FU) is a pyrimidine analog that inhibits thymidylate synthase, interfering with DNA synthesis. It is metabolized to its active metabolites, which incorporate into RNA and DNA, causing cytotoxicity primarily in S-phase cells.
Folate antimetabolite; inhibits dihydrofolate reductase (DHFR), blocking conversion of dihydrofolate (DHF) to tetrahydrofolate (THF), thereby inhibiting DNA synthesis, repair, and cellular replication. Also inhibits thymidylate synthetase and purine synthesis.
12 mg/kg IV bolus daily for 4 days, then if no toxicity, 6 mg/kg IV on days 6, 8, 10, and 12; or 15 mg/kg IV weekly; or 500-600 mg/m2 IV every 3-4 weeks.
7.5-25 mg orally once weekly; alternatively, 10-25 mg intramuscularly, intravenously, or subcutaneously once weekly.
None Documented
None Documented
Clinical Note
moderateMethotrexate + Digoxin
"Methotrexate may decrease the cardiotoxic activities of Digoxin."
Clinical Note
moderateMethotrexate + Digitoxin
"Methotrexate may decrease the cardiotoxic activities of Digitoxin."
Clinical Note
moderateMethotrexate + Deslanoside
"Methotrexate may decrease the cardiotoxic activities of Deslanoside."
Clinical Note
moderateMethotrexate + Acetyldigitoxin
"Methotrexate may decrease the cardiotoxic activities of Acetyldigitoxin."
Biphasic elimination: initial t1/2α ~10-20 minutes, terminal t1/2β ~20-24 hours. Accumulation occurs with continuous infusion.
Terminal half-life: 3-10 hours (low dose) to 8-15 hours (high dose); clinical context: prolonged to 24-48 hours in renal impairment, third-space effusions, or polyglutamation. Delayed elimination due to enterohepatic recirculation.
Primarily hepatic metabolism; renal excretion of metabolites accounts for ~60-80% of the dose. Unchanged fluorouracil excreted renally is <10%. Fecal excretion is minimal (<5%).
Renal: 80-90% unchanged via glomerular filtration and tubular secretion; biliary/fecal: <10% as metabolites (7-hydroxymethotrexate).
Category C
Category D/X
Antimetabolite
Antimetabolite