Pharmacokinetics of oxaliplatin in humans

  title={Pharmacokinetics of oxaliplatin in humans},
  author={Hans Ehrsson and Inger Wallin and Jeffrey Yachnin},
  journal={Medical Oncology},
Oxaliplatin is a novel platinum complex used for the treatment of metastatic colorectal carcinoma. The pharmacokinetics of the free fraction of oxaliplatin in blood were evaluated in 10 patients given 85 mg/m2 of oxaliplatin using an infusion time of 2 h. Blood samples were collected during and after the infusion and immediately placed on ice. The samples were ultrafiltrated centripetally and the concentration of oxaliplatin in the ultrafiltrate was determined by liquid chromatography in… 

Pharmacokinetics of oxaliplatin in patients with severe hepatic dysfunction

The comparable platinum exposure early after administration in conjunction with the lack of acute toxicity do not support a dose reduction of oxaliplatin in patients with markedly elevated bilirubin concentrations, but a larger number of patients must be examined before valid dose recommendations can be derived.

Oxaliplatin Pharmacokinetics and Pharmacodynamics in Adult Cancer Patients with Impaired Renal Function

Oxali Platin pharmacokinetics are altered in patients with renal impairment, but a corresponding increase in oxaliplatin-related toxicities is not observed.

Systemic exposure of the parent drug oxaliplatin during hyperthermic intraperitoneal perfusion

The systemic exposure of oxaliplatin measured after HIPEC using a selective analytical technique is considerably lower than previously reported results obtained by atomic absorption spectroscopy.

Pharmacokinetics and Toxicodynamics of Oxaliplatin in Rats: Application of a Toxicity Factor to Explain Differences in the Nephrotoxicity and Myelosuppression Induced by Oxaliplatin and the Other Platinum Antitumor Derivatives

The product of AUCp and the toxicity factor is a useful predictor of the degree of toxicity of oxaliplatin as has been observed with other platinum drugs.

Dose-banding studies on oxaliplatin

Dose-banding with the +10% maximum deviation was selected as the most promising dosing scheme for oxaliplatin and safety and efficacy of vii dose- banding schemes was demonstrated by comparing the simulated PK characteristics gained from the ex vivo model.


The chemistry of oxaliplatin, a platinum-based cytostatic drug used in combination with 5fluorouracil and leucovorin for palliative and adjuvant treatment of metastatic colorectal cancer, is elucidated and it has been proposed that the acute neurotoxic side effects of oxalaplatin treatment involve voltage-gated ion channels.

Oxaliplatin: a review of approved uses

Oxaliplatin has proven beneficial in the treatment of CRC and can currently be regarded as one of the three most important chemotherapeutic drugs used in the Treatment of both metastatic disease and adjuvant therapy in stage II/III after resection.

Oxaliplatin degradation in the presence of important biological sulphur-containing compounds and plasma ultrafiltrate.

Pharmacodynamics of Oxaliplatin-Derived Platinum Compounds During Hyperthermic Intraperitoneal Chemotherapy (HIPEC): An Emerging Aspect Supporting the Rational Design of Treatment Protocols

The bioactivity of peritoneal perfusates ex vivo is a useful parameter for evaluating the actual cytotoxic potential of OX and its derivatives used in HIPEC over time, overcoming important limitations and disadvantages associated with respective drug monitoring only.



Oxaliplatin pharmacokinetics during a four-hour infusion.

On the basis of the simulation of the plasma levels and the urinary excretion of platin following the long-term administration of oxaliplatin as a constant-rate and a chronomodulated infusion, additional analyses are warranted to fully characterize the pharmacokinetics of the drug in these settings.

Clinical pharmacokinetics of oxaliplatin: a critical review.

These results indicate that the additive/synergistic antitumor activity observed with oxaliplatin, 5-fluorouracil, and irinothecan is not due to major alterations in drug exposure, and the enhanced efficacy is likely to be mechanistically based.

Pharmacokinetics of oxaliplatin in patients with normal versus impaired renal function

This study failed to elicit any relationship between moderate renal impairment and the acute toxicity associated with oxaliplatin, and results are in agreement with the in vitro data concerning the extensive binding of oxali Platin to plasma proteins and RBCs.

Early biotransformations of oxaliplatin after its intravenous administration to cancer patients.

It is demonstrated that in the first hours after its infusion, oxaliplatin, in addition to other Pt compounds, is present in plasma and urine and that Pt is bound to albumin, gamma-globulins, and hemoglobin.

Biotransformations of oxaliplatin in rat blood in vitro

Pt‐dach complexes appeared to be taken up better by RBCs than cisplatin or carboplatin, and the hydrophobicity of most of the Pt‐daches appeared to correlate with uptake, however, factors other than the dach carrier ligand and hydrophOBicity clearly influence uptake.

Pharmacokinetics of cisplatin and its monohydrated complex in humans.

The pharmacokinetics of cisplatin and its cytotoxic hydrolysis product cis-diammineaquachloroplatinum(II) ion (monohydrated complex) were investigated in seven patients after they received a 1-h infusion of cis platin in normal saline at 100 mg/m2 and it was concluded that the significant amounts of the monohydratedcomplex present in blood are due to the fraction already present in the administered dose and to the fractions formed in blood.

Oxaliplatin clinical activity: a review.

Stability of cisplatin and its monohydrated complex in blood, plasma and ultrafiltrate--implications for quantitative analysis.

Cytotoxicity, cellular uptake, and cellular biotransformations of oxaliplatin in human colon carcinoma cells.

The data suggest that intracellular conversion of oxaliplatin to Pt(dach)Cl2 makes only a minor contribution to Pt-DNA adduct formation and the resultant cytotoxicity of oxalaplatin.

Oxaliplatin-induced damage of cellular DNA.

It is demonstrated that oxaliplatin-induced DNA lesions, including ISC and DPC, are likely to contribute to the drug's biological properties and requires fewer DNA lesions than does cisplatin to achieve cell growth inhibition.