title: Toxicity and pharmacokinetics of isolated lung perfusion with cisplatin in rat.
abstract: OBJECTIVE
  This study was designed to evaluate the toxicity and the pharmacokinetics of cisplatin administered via isolated lung perfusion in Fischer 344 rat.
  
  
  METHODS
  Toxicity study; Cisplatin dosages of 3.3, 5.0, 6.7, and 10.0 mg/kg were injected intravenously in four groups, respectively. Cisplatin dosages of 3.3, 5.0, and 6.7 mg/kg were perfused via isolated lung perfusion in a further three groups, respectively. The maximum tolerated dosage of cisplatin was determined by assessing the survival rate on day 21. Pharmacokinetics study; Animals received 6.7 mg/kg of cisplatin intravenously or 3.3 mg/kg of cisplatin via isolated lung perfusion. The cisplatin levels of the lung were measured by flameless atomic spectrometry.
  
  
  RESULTS
  Toxicity study; The maximum tolerated dosage of cisplatin via intravenous injection was 6.7 mg/kg, and via isolated lung perfusion was 3.3 mg/kg. Pharmacokinetics study; The cisplatin level in the perfused lung was significantly higher than that in the lung of the animal treated intravenously (16.6 +/- 6.2 micrograms/g of tissue and 7.5 +/- 3.2 micrograms/g of tissue, respectively) (p = 0.0096).
  
  
  CONCLUSIONS
  Isolated lung perfusion with 3.3 mg/kg of cisplatin was pharmacokinetically superior to the maximum tolerated intravenous injection of cisplatin.
authors.affiliation: Department of Surgery I, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneda
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Brooks
authors.forename: A
authors.initials: A
authors.lastname: Abolhoda
authors.forename: D
authors.initials: D
authors.lastname: Labow
authors.forename: M E
authors.initials: ME
authors.lastname: Burt
authors.forename: R J
authors.initials: RJ
authors.lastname: Ginsberg
mesh_terms: D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D004361:Drug Tolerance; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002945:Cisplatin