Pharmacokinetics of hypotonic cisplatin chemotherapy administered into the peritoneal and the pleural cavities in experimental model.
The pharmacokinetics of intraperitoneal (i.p.) and intrapleural (i.pl.) hypotonic cisplatin (CDDP) were compared under the same experimental conditions. The same dose of CDDP was administered in hypotonic (62 mOsm/L) and isotonic (308 mOsm/L) solutions to the peritoneal and pleural cavities of Ehrlich carcinoma cell bearing mice. The intracellular amount of platinum increased for more than 60 minutes after an i.pl. injection of the hypotonic solution of CDDP, whereas it increased for up to 30 minutes after an i.p. injection. Although hypotonic conditions augmented the amount of platinum taken-up by Ehrlich cells, the amount was significantly greater in the pleural cavity than in the peritoneal cavity. In Donryu rats, the levels of platinum in the i.p. and i.pl. fluids decreased rapidly after injection of hypotonic solution as compared with isotonic solution. The extent of this decrease was greater in the peritoneal cavity than in the pleural cavity. In the hypotonic condition, the area under the curve of concentration versus time (AUC) for platinum of i.pl. fluid was greater than that of i.p. fluid. When i.p. and i.pl. hypotonic CDDP were administered, the osmolarity of the fluid returned rapidly to the isotonic level, with equilibration in 30 or 180 minutes respectively. The lower osmolarity continued for a longer duration in the pleural cavity than in the peritoneal cavity. These results indicate that the pleural cavity may require a smaller amount of CDDP to achieve the same effect on intracellular uptake of platinum than the peritoneal cavity.
Department of Surgery I, Faculty of Medicine, Tottori University, Yonago, Japan. surgeryI@grape.med.tottori-u.ac.jp
K
K
Katano
S
S
Tsujitani
S
S
Oka
H
H
Saito
Y
Y
Gomyo
A
A
Kondo
M
M
Ikeguchi
M
M
Maeta
N
N
Kaibara
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002945:Cisplatin / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009994:Osmolar Concentration; D010529:Peritoneal Cavity / Q000502:physiology*; D010994:Pleura / Q000378:metabolism*; D051381:Rats
D000970:Antineoplastic Agents; D002945:Cisplatin