Oxaliptatin for Injection
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Name: Oxaliplatin for Injection
Mechanism of Action
Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. Both inter- and intra-strand Pt-DNA cross-links are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG) , adjacent adenine-guanines (AG) , and guanines separated by an intervening nucleotide (GNG) . These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific.
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 (colon) , GR (mammary) , and L1210 (leukemia) ].
The reactive oxaliplatin derivatives are present as a fraction of the unbound platinum in plasma ultrafiltrate. The decline of ultrafilterable platinum levels following oxaliplatin administration is triphasic, characterized by two relatively short distribution phases (t1/2(Alpha) ; 0.43 43hours and t1/2(Beta) ; 16.8 hours) and a long terminal elimination phase (t1/2γ ; 391 hours) . Pharmacokinetic parameters obtained after a single 2-hour IV infusion of ELOXATIN at a dose of 85 mg/m2 expressed as ultrafilterable platinum were Cmax of 0.814 5g/mL and volume of distribution of 440 L. Interpatient and intrapatient variability in ultrafilterable platinum exposure (AUC0-48)
assessed over 3 cycles was moderate to low (23% and 6%, respectively) . A pharmacodynamic relationship between platinum ultrafiltrate levels and clinical safety and effectiveness has not been established.