Henplatin Mechanism of Action

Pharmacology: Oxaliplatin has toxicities commonly seen in platinum compounds and exhibits category-specific cardiac toxicity. No renal toxicity of cisplatin or bone marrow toxicity was observed. A relatively new platinum compound, it acts on DNA by producing alkylation conjugate and forms inter- and intrastrand Pt-DNA crosslinks, consequently, inhibits synthesis and replication of DNA. It rapidly combines with DNA, at most 15 min. Combination of cisplatin and DNA is divided into phases, which includes a delay phase after 48 hrs [In vivo, an hr after administration, determine presence of conjugate of adduct of leukocyte. DNA synthesis during replication, DNA separation after replication, synthesis of RNA and cell protein is inhibited]. It is effective for some cell lines resistant to cisplatin.
Pharmacokinetics: After 2 hrs of continuous infusion at a dose of 130 mg/m², the total plasma platinum reaches peak value of 5.1±0.8 mg/mL/hr, the stimulant AUC is 189±45 mg/mL/hr. After infusion, 50% of platinum combine with erythrocyte and the other 50% of platinum is present in plasma. 25% of plasma platinum is in free form; the other 75% plasma platinum combine with protein. Protein-combined platinum increases gradually and reaches stable level of 95%, 5 days after administration. The clearance is divided into 2 phases; the t_½ of clearance phase is about 40 hrs. Up to 50% of platinum is eliminated via urine within 48 hrs (55% of platinum is cleared in 6 days). Fecal excretion is limited (only 5% of platinum is eliminated through feces in 11 days). In patients with renal failure, only clearance of filterable platinum decreases and thus no dosage adjustment is necessary.
At 22nd day after administration, the level of erythrocyte-bonded platinum is 56% of plasma peak value, while at the same time, most plasma platinum have been eliminated. During latter administration periods, no significant increase in the levels of total plasma or plasma platinum was observed while erythrocyte-bonded platinum cumulative evidence.