Population pharmacokinetics of hyperthermic intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis after cytoreductive surgery
Abstract: PURPROSE: To characterize the hyperthermic intraperitoneal oxaliplatin (HIO) pharmacokinetics in peritoneum and plasma in patients with peritoneal carcinomatosis (PC) after cytoreductive surgery (CRS). METHODS: Data from 36 patients receiving HIO diluted in isotonic 4 % icodextrin were combined with data from 13 patients receiving HIO diluted in isotonic 5 % dextrose. Total oxaliplatin in peritoneal and plasma fluids were used to characterize an open two-compartment disposition model with linear distribution and elimination and first-order absorption from peritoneum to plasma using NONMEM software. The effect of patient- and treatment-related covariates on oxaliplatin pharmacokinetic parameters was explored. RESULTS: The typical value (interindividual variability, %) in ka, CL, and Vss were 0.57 h−1 (43 %), 1.71 L h−1 (39 %), and 77 L (65 %), respectively. No significant effect of age, body surface area, sex, creatinine clearance, liver metastases, PC index, and complete cytoreduction on pharmacokinetic parameters was found. A 12–15 % reduction in peritoneal volume of distribution was observed in patients receiving HIO diluted in 5 % dextrose relative to those patients receiving HIO diluted in 4 % icodextrin. CONCLUSIONS: The integration of peritoneal and plasma data demonstrated oxaliplatin linear absorption from peritoneum to plasma, non-specific distribution to a peripheral compartment, and linear elimination from the central compartment when HIO was administered with isotonic carrier solutions to PC patients who underwent CRS. Only the effect of the carrier solution had an impact in the peritoneal volume of distribution, but its clinical relevance seems to be limited, especially for short HIO infusions (
Full Reference: Perez-Ruixo, Carlos, Belen Valenzuela, Jose Esteban Peris, Pedro Bretcha-Boix, Vanesa Escudero-Ortiz, Jose Farre-Alegre, and Juan Jose Perez-Ruixo. “Population Pharmacokinetics of Hyperthermic Intraperitoneal Oxaliplatin in Patients with Peritoneal Carcinomatosis after Cytoreductive Surgery.” Cancer Chemotherapy and Pharmacology 71, no. 3 (March 2013): 693–704. doi:10.1007/s00280-012-2060-2.
Link to full text: http://link.springer.com/article/10.1007%2Fs00280-012-2060-2