title: Population pharmacokinetics of hyperthermic intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis after cytoreductive surgery.
abstract: OBJECTIVE
  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 k(a), CL, and V(ss) 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 (<60 min).
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, University of Valencia, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Ruixo
authors.forename: Belén
authors.initials: B
authors.lastname: Valenzuela
authors.forename: José Esteban
authors.initials: JE
authors.lastname: Peris
authors.forename: Pedro
authors.initials: P
authors.lastname: Bretcha-Boix
authors.forename: Vanesa
authors.initials: V
authors.lastname: Escudero-Ortiz
authors.forename: José
authors.initials: J
authors.lastname: Farré-Alegre
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Pérez-Ruixo
mesh_terms: D000368:Aged; D000465:Algorithms; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006207:Half-Life; D006801:Humans; D006979:Hyperthermia, Induced; D007274:Injections, Intraperitoneal; D007813:Laparotomy; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D010537:Peritoneum / Q000378:metabolism; D019999:Pharmaceutical Solutions; D011153:Population; D012984:Software
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D019999:Pharmaceutical Solutions; D000077150:Oxaliplatin