Pharmacokinetics of heated intraperitoneal oxaliplatin

Ferron, Gwénaël; Dattez, S.; Gladieff, L.; Delord, Jean‐Pierre; Plutniak, Sébastien; Lafont, Thierry; Lochon, Isabelle; Chatelut, Étienne

doi:10.1007/s00280-007-0654-x

Cited by 30 publications

(32 citation statements)

References 7 publications

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“…[9]). The mean elimination half-life in the perfusate and the percent dose absorbed were in general agreement with previous results [6,7], which is to be expected since the major Pt-containing agent in the perfusate is intact oxaliplatin. Patients with higher BMI showed increased absorption of oxaliplatin, which might be due to a larger peritoneum surface area.…”

Section: Discussionsupporting

confidence: 91%

“…The systemic exposure of oxaliplatin was about four times lower than previously reported in studies analysing ultrafiltrated platinum by using AAS [6,7]. This is due to the fact that, with time, intact oxaliplatin will constitute a gradually decreasing fraction of total ultrafiltrated Pt due to its high chemical reactivity with endogenous compounds [16].…”

Section: Discussionmentioning

confidence: 74%

“…The pharmacokinetics of oxaliplatin during HIPEC has so far only been studied using the unselective analytical technique of AAS measuring the total platinum content [6,7]. Since oxaliplatin rapidly reacts with endogenous sulphur compounds [16] forming a variety of reaction products, AAS will overestimate the concentration of the active drug.…”

Section: Discussionmentioning

confidence: 99%

“…Oxaliplatin, a third-generation antineoplastic platinum complex, is currently used in the treatment of advanced colorectal cancer. Previous kinetic studies of oxaliplatin during HIPEC have been based on the use of atomic absorption spectroscopy (AAS), an unselective analytical technique measuring the total platinum content in plasma ultrafiltrate or plasma [6,7]. This method will codetermine oxaliplatin and platinum (Pt)-containing cytotoxic and biologically inactive biotransformation products.…”

Section: Introductionmentioning

confidence: 99%

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Systemic exposure of the parent drug oxaliplatin during hyperthermic intraperitoneal perfusion

Mahteme

Wallin

Glimelius

et al. 2008

Eur J Clin Pharmacol

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Objective To evaluate the perfusate and systemic kinetics of oxaliplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) using a selective analytical technique. Methods HIPEC was carried out in eight patients by the open abdomen coliseum technique for 30 min at 41.5-43°C with an average of 427 mg/m 2 of oxaliplatin in 5% dextrose solution. Blood and perfusate samples were collected during the perfusion. Additional blood samples were taken up to 2 h after the end of perfusion. The analysis was performed by liquid chromatography and post-column derivatization with N,N-diethyldithiocarbamate using microwave heating. Results The mean elimination half-life of oxaliplatin in the perfusate was 29.5 min (range 21.1-41.2 min) and in the peripheral circulation 24.7 min (range 21.7-27.7 min). The ratio of the areas under the time concentration curve in perfusate and blood was 12.8±2.9. ConclusionThe systemic exposure of oxaliplatin measured after HIPEC using a selective analytical technique is considerably lower than previously reported results obtained by atomic absorption spectroscopy.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Systemic exposure of the parent drug oxaliplatin during hyperthermic intraperitoneal perfusion

Mahteme

Wallin

Glimelius

et al. 2008

Eur J Clin Pharmacol

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“…Several phase I dose-escalation studies in PC patients treated with CRS have characterized the HIO pharmacokinetics in both the peritoneum and plasma (14)(15)(16). Following 460 mg/m 2 dosing, the maximum HIO concentration (C max ) in the peritoneum (330 mg/L) (16) was 130-fold higher than plasma C max (2.59 mg/L) after intravenous (IV) administration of 130 mg/m 2 (17), indicating that, relative to IV dosing, HIO administration after CRS delivers a higher peritoneal oxaliplatin exposure with a minimum access to the systemic circulation, that limits the hematological toxicities, such as thrombocytopenia and neutropenia, which are the oxaliplatin dose-limiting toxicities after IV dosing (18).…”

Section: Introductionmentioning

confidence: 99%

Platelet Dynamics in Peritoneal Carcinomatosis Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Oxaliplatin

Pérez-Ruixo

Valenzuela

Peris

et al. 2015

AAPS J

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Abstract. The aim of the study was to characterize the platelet count (PLT) dynamics in peritoneal carcinomatosis patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal oxaliplatin (HIO). Data from patients treated with CRS alone (N=18) or CRS and HIO (N=62) were used to estimate the baseline platelet count (PLT 0 ), rate constants for platelet maturation (k tr ) and platelet random destruction (k s ), feedback on progenitor cell proliferation (γ), and the drug-specific model parameters (α, β). Plasma oxaliplatin concentrations, C p , reduced the proliferation rate of progenitor cells (k prol ) according to a power function α×C p β . The surgery effect on k prol and k s was explored. The typical values (between subject variability) of the PLT 0 , k tr , k s , γ, α, and β were estimated to be 237×10 9 cells/L (32.9%), 7.09×10 −3 h −1 (47.1%), 8.86×10 −3 h −1 (80.0%), 0.621, 0.88 L/mg (56.9%), and 2.63. Surgery induced a maximal 2.09-fold increase in k prol that was attenuated with a half-life of 8.42 days. Splenectomy decreased k s by 47.5%. Age, sex, body surface area, sex, total proteins, and HIO carrier solution did not impact the model parameters. The model developed suggests that, following CRS and HIO, thrombocytopenia and thrombocytosis were reversible and short-lasting; the severity of the thrombocytopenia and thrombocytosis was inversely correlated, with splenectomized patients having thrombocytopenia of lower severity and thrombocytosis of higher severity; and the HIO dose and treatment duration determine the severity and duration of the thrombocytopenia. Higher HIO dose or longer treatment duration could be used without substantially increasing the risk of major hematological toxicity.

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