Pharmacokinetics of hypotonic cisplatin chemotherapy administered into theperitoneal and the pleural cavities in experimental model

The pharmacokinetics of intraperitoneal (i.p.) and intrapleural (i.pl.) hyp otonic cisplatin (CDDP) were compared under the same experimental condition s. The same dose of CDDP was administered in hypotonic (62 mOsm/L) and isot onic (308 mOsm/L) solutions to the peritoneal and pleural cavities of Ehrli ch carcinoma cell bearing mice. The intracelluar amount of platinum increas ed for more than 60 minutes after an i.pl.. injection of the hypotonic solu tion of CDDP, whereas it increased for up to 30 minutes after an i.p. injec tion. Although hypotonic conditions augmented the amount of platinum taken- up by Ehrlich cells, the amount was significantly greater in the pleural ca vity 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 w as greater in the peritoneal cavity than in the pleural cavity. In the hypo tonic 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 ip, and i.pl. hypotonic CDDP were administered, the osmolality of the fluid re turned rapidly to the isotonic level, with equilibration in 30 or 180 minut es respectively. The lower osmolarity continued for a longer duration in th e pleural cavity than in the peritoneal cavity. These results indicate that the pleural cavity may require a smaller amount of CDDP to achieve the sam e effect on intracellular uptake of platinum than the peritoneal cavity.