Intrapleural administration of lipoplatin in an animal model.
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.
Froudarakis
Marios E
ME
Department of Pneumonology, Medical School Democritus University of Thrace, Greece. mfroud@med.duth.gr
Greillier
Laurent
L
Monjanel-Mouterde
Suzanne
S
Koutsopoulos
Anastassios
A
Devictor-Pierre
Benedicte
B
Guilhaumou
Romain
R
Karpathiou
Georgia
G
Botaitis
Sotirios
S
Astoul
Philippe
P
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
D000970:Antineoplastic Agents; C503131:lipoplatin; D002945:Cisplatin