| Indication |
Used in combination with infusional 5-FU/LV, is indicated for the
treatment of advanced carcinoma of the colon or rectum and for adjuvant
treatment of stage III colon cancer patients who have undergone complete
resection of the primary tumor. |
| Pharmacodynamics |
Oxaliplatin selectively inhibits the synthesis of
deoxyribonucleic acid (DNA). The guanine and cytosine content correlates
with the degree of Oxaliplatin-induced cross-linking. At high
concentrations of the drug, cellular RNA and protein synthesis are also
suppressed. |
| Mechanism of action |
After activation, oxaliplatin binds preferentially to the guanine
and cytosine moieties of DNA, leading to cross-linking of DNA, thus
inhibiting DNA synthesis and function. |
| Absorption |
Bioavailability is complete following intravenous administration. |
| Volume of distribution |
|
| Protein binding |
Plasma protein binding of platinum (active metabolite) is irreversible and is greater than 90%. |
| Metabolism |
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. There is no evidence of cytochrome P450-mediated
metabolism in vitro. |
| Route of elimination |
The major route of platinum elimination is renal excretion. At
five days after a single 2-hour infusion of oxaliplatin, urinary
elimination accounted for about 54% of the platinum eliminated, with
fecal excretion accounting for only about 2%. |
| Half life |
Approximately 10 - 25 minutes |
| Clearance |
Not Available |
| Toxicity |
There have been five cases of oxaliplatin overdose reported. One
patient received two 130 mg/m2 doses of oxaliplatin (cumulative dose of
260 mg/m2) within a 24-hour period. The patient experienced Grade 4 thrombocytopenia (<25,000/mm3)
without any bleeding, which resolved. Two other patients were
mistakenly administered oxaliplatin instead of carboplatin. One patient
received a total oxaliplatin dose of 500 mg and the other received 650
mg. The first patient experienced dyspnea, wheezing, paresthesia,
profuse vomiting and chest pain on the day of administration. She
developed respiratory failure and severe bradycardia, and subsequently
did not respond to resuscitation efforts. The other patient also
experienced dyspnea, wheezing, paresthesia, and vomiting. |
