title: Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study.
abstract: BACKGROUND
  Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis.
  
  
  METHODS
  Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM.
  
  
  RESULTS
  Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity.
  
  
  CONCLUSIONS
  This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.
authors.affiliation: CHU Besançon, Department of Pharmacology, Laboratoire de Pharmacologie Clinique-CHU Jean Minjoz-bvd Fleming, Besançon Cedex F25030, France. broyer@chu-besancon.fr
authors.forename: B
authors.initials: B
authors.lastname: Royer
authors.forename: E
authors.initials: E
authors.lastname: Kalbacher
authors.forename: S
authors.initials: S
authors.lastname: Onteniente
authors.forename: V
authors.initials: V
authors.lastname: Jullien
authors.forename: D
authors.initials: D
authors.lastname: Montange
authors.forename: S
authors.initials: S
authors.lastname: Piedoux
authors.forename: A
authors.initials: A
authors.lastname: Thiery-Vuillemin
authors.forename: D
authors.initials: D
authors.lastname: Delroeux
authors.forename: S
authors.initials: S
authors.lastname: Pili-Floury
authors.forename: E
authors.initials: E
authors.lastname: Guardiola
authors.forename: M
authors.initials: M
authors.lastname: Combe
authors.forename: P
authors.initials: P
authors.lastname: Muret
authors.forename: V
authors.initials: V
authors.lastname: Nerich
authors.forename: B
authors.initials: B
authors.lastname: Heyd
authors.forename: B
authors.initials: B
authors.lastname: Chauffert
authors.forename: J-P
authors.initials: JP
authors.lastname: Kantelip
authors.forename: X
authors.initials: X
authors.lastname: Pivot
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004837:Epinephrine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007432:Intraoperative Period; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D010537:Peritoneum / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D002945:Cisplatin; D004837:Epinephrine