A study of cis-diamminedichloroplatinum(II) suppositories for the treatment of rabbit uterine endometrial carcinoma.
cis-Diamminedichloroplatinum (II) (cisplatin: CDDP) suppositories containing NaCl at different concentrations were prepared as a local chemotherapeutic agent for the treatment of uterine endometrial carcinoma and were administered to rabbits implanted with uterine VX2 tumor. The intrauterine CDDP histological level, as well as the antitumor effects and side effects of the suppositories to the liver and kidney were studied. The results showed high intrauterine tissue CDDP level in all suppository administrations. In particular, the NaCl-added suppositories enhanced the intrauterine CDDP level. As for antitumor effects, while the tumor growth rate of the NaCl-added suppository group was likely to be suppressed, the suppositories could not suppress tumor growth completely. The plasma platinum (Pt) level was 1.5 micrograms/ml or less and that of the liver and kidney was as low as 0.31 to 0.48 micrograms/g. No difference in levels depending on NaCl concentration was observed, nor was any abnormality found in the biochemical analysis including glutamate oxaloacetate transaminase (GOT) and blood urea nitrogen (BUN). Histopathological study revealed the degeneration of tumor cells in the NaCl-added suppository group. Minimal congestion and hemorrhage were observed in the endometria, possibly resulting from CDDP. By adding NaCl to CDDP suppositories, the uterine CDDP level and antitumor effects increased while no serious renal dysfunction was noted. Therefore, we conclude that NaCl-added CDDP suppositories are a useful local chemotherapy for endometrial carcinoma.
Kyotani
S
S
Department of Pharmacy, Kochi Medical School Hospital, Japan.
Nishioka
Y
Y
Kusunose
M
M
Tanaka
T
T
Hamada
T
T
Yamanaka
S
S
Sagara
Y
Y
Ogiso
T
T
Tanada
S
S
Terao
M
M
D000818:Animals; D002626:Chemistry, Pharmaceutical; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004355:Drug Stability; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D011817:Rabbits; D012965:Sodium Chloride / Q000494:pharmacology; D013237:Stereoisomerism; D013488:Suppositories; D014018:Tissue Distribution; D014599:Uterus / Q000378:metabolism
D003692:Delayed-Action Preparations; D013488:Suppositories; D012965:Sodium Chloride; D002945:Cisplatin