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Pharmacology: In vivo studies have shown antitumor activity of oxaliplatin against colon carcinoma. In combination with 5-fluorouracil (5-FU), oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models [HT29 (colon), GR (mammary) and L1210 (leukemia)].
Mechanism of Action: Oxaliplatin (Zildox) undergoes nonenzymatic on physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo DACH platinum, which covalently bind with macromolecules. Both inter- and intrastrand Pt-DNA cross-links are formed between the N7 positions of two adjacent guanines (GG).
These cross links inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific.
Pharmacokinetics: Distribution: At the end of a 2-hour infusion of oxaliplatin for injection, approximately 15% of the administered platinum is present in the systemic circulation. The remaining 85% is rapidly distributed into tissues or eliminated in the urine.
Metabolism: Oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation. There is no evidence of cytochrome P450-mediated metabolism in vitro.
Elimination: The active metabolite of oxaliplatin (Zildox) are DACH platinum species. Oxaliplatin is excreted mainly by renal excretion. Approximately 50% of the administered dose is excreted in the urine within the first 3 days. Fecal excretion is approximately 0.5% per day and reaches 5% of the total body dose by day 11. The terminal half-life of ultrafiltration platinum (oxaliplatin and free oxaliplatin metabolites) is 273+19 hrs. The platinum elimination from the erythrocytes takes about 48 days.
