title: Intrapleural administration of lipoplatin in an animal model.
abstract: BACKGROUND
  Lipoplatin is a new liposomal cisplatin already tested in solid tumors with encouraging results. Little is known about the activity of lipoplatin administered intrapleurally (IP).
  
  
  OBJECTIVE
  The aim of this study was to assess in an animal model the pharmacokinetics, and potentially induced histopathological lesions of lung and kidney after IP vs. IV injection of lipoplatin.
  
  
  METHODS
  15 male Wistar rats were assigned to an IV group at dose 10mg/kg of lipoplatin (group 1) and to IP groups at 10 (group 2) or 20mg/kg (group 3) equal to 60 and 120 mg/m(2) in humans respectively. After lipoplatin administration, serial plasma samples were analyzed by atomic absorption spectrometry for the maximum plasma concentration (C(max)), the area under the plasma concentration-time curve (AUC), and the total body clearance (CL). Pleura, lungs and kidneys of the rats were histologically examined for possible lesions.
  
  
  RESULTS
  The C(max) was significantly higher in groups 1 vs. 2 (p = 0.02) and vs. 3 (p = 0.01). The AUC of groups 3 vs. 1 was significantly higher (p = 0.028) but the AUC of groups 2 vs. 1 was significantly lower (p = 0.02). CL in IP rats did not differ considerably compared to the IV. Inflammatory changes were noted in the pleura of IP rats and mild kidneys lesions in IV group.
  
  
  CONCLUSIONS
  Compared to the IV route, IP20 administration of lipoplatin yielded higher AUC, equal CL, but a significantly lower C(max). As C(max) is a determinant of lipoplatin toxicity, IP administration might offer a more effective therapeutic index while improving tolerability. We noted fibrotic changes in the pleura of IP rats, and mild kidneys changes in IV rats, as expected.
authors: Department of Pneumonology, Medical School Democritus University of Thrace, Greece. mfroud@med.duth.gr
authors: Marios E
authors: ME
authors: Froudarakis
authors: Laurent
authors: L
authors: Greillier
authors: Suzanne
authors: S
authors: Monjanel-Mouterde
authors: Anastassios
authors: A
authors: Koutsopoulos
authors: Benedicte
authors: B
authors: Devictor-Pierre
authors: Romain
authors: R
authors: Guilhaumou
authors: Georgia
authors: G
authors: Karpathiou
authors: Sotirios
authors: S
authors: Botaitis
authors: Philippe
authors: P
authors: Astoul
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D007267:Injections; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; C503131:lipoplatin; D002945:Cisplatin