title: Pharmacologic advantages of negative-balance isolated pelvic perfusion: achievement of intensive exposure of the pelvis to platinum without systemic leakage.
abstract: OBJECTIVE
  To study tissue platinum concentrations and the correlation between tissue and plasma platinum concentrations after negative-balance isolated pelvic perfusion (NIPP) in a porcine model.
  
  
  METHODS
  All animal experiments were conducted according to the University Guidelines for Animal Care and Experimentation. Cisplatin (5 mg per kilogram of body weight) was administered into balloon catheter-isolated porcine pelvic circulations (n=7) and also systemically to a control group (n=7). Platinum concentrations in pelvic blood, systemic blood, urine, pelvic tissues (uterus, bladder, lymph nodes, and muscles), and kidneys were measured. Maximum platinum concentration (maximum serum drug concentration [C-max]) and area under the blood concentration-time curve (AUC) were compared between the two groups.
  
  
  RESULTS
  With NIPP, pelvic C-max (58.4 mg/L) and AUC (1163.6 mg⋅min/L) were 44.9- and 56.2-fold higher than systemic C-max (1.3 mg/L) and AUC (20.7 mg⋅min/L), respectively, whereas the corresponding values in the control group were almost identical. Tissue platinum concentrations in pelvic organs were 2.8-5.6-fold higher than the control values. Platinum concentrations in kidney tissue were markedly lower with NIPP (1.0 mg/L) compared with the controls (8.1 mg/L). High platinum concentrations in pelvic tissues correlated well (P<.01) with high pelvic C-max and AUC.
  
  
  CONCLUSIONS
  The pharmacologic advantages of NIPP were evident, with achievement of high platinum C-max, AUC, and high pelvic tissue concentrations without exposing systemic organs to platinum.
authors.affiliation: Department of Radiology/Center for Advanced Medical Technology, Nippon Medical School, and Tokyo Labor-Welfare Hospital, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan. genji@nms.ac.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Murata
authors.forename: Shiro
authors.initials: S
authors.lastname: Onozawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oda
authors.forename: Takahiko
authors.initials: T
authors.lastname: Mine
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ueda
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kumita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nomura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D005112:Extracorporeal Circulation / Q000379:methods*; D005260:Female; D009928:Organ Specificity; D010388:Pelvis / Q000098:blood supply*; D010477:Perfusion / Q000379:methods*; D013552:Swine; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin