title: Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy.
abstract: BACKGROUND
  Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia.
  
  
  METHODS
  We collected blood and peritoneal perfusate samples from ten patients undergoing HIPEC with a BSA-based dose of 250 mg/m(2) oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. We monitored blood glucose for 24 h postoperatively. Areas under concentration-time curves (AUC) were calculated by trapezoidal rule. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/AUC[plasma]). We used linear regression to test for statistical significance.
  
  
  RESULTS
  Higher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels.
  
  
  CONCLUSIONS
  Higher BSA is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration. Plasma glucose levels after oxaliplatin HIPEC were not clearly related to BSA.
authors: Division of Medical Oncology, Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors: Joshua C
authors: JC
authors: Leinwand
authors: Gleneara E
authors: GE
authors: Bates
authors: John D
authors: JD
authors: Allendorf
authors: John A
authors: JA
authors: Chabot
authors: Sharyn N
authors: SN
authors: Lewin
authors: Robert N
authors: RN
authors: Taub
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D001202:Ascitic Fluid / Q000378:metabolism; D001830:Body Surface Area; D010478:Chemotherapy, Cancer, Regional Perfusion; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008654:Mesothelioma / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000097:blood / Q000493:pharmacokinetics*; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy*; D011379:Prognosis; D011553:Pseudomyxoma Peritonei / Q000473:pathology / Q000628:therapy*; D012710:Serum Albumin, Bovine / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D012710:Serum Albumin, Bovine