Intra-hepatic arterial administration with miriplatin suspended in an oily lymphographic agent inhibits the growth of tumors implanted in rat livers by inducing platinum-DNA adducts to form and massive apoptosis.
BACKGROUND
Miriplatin (formerly SM-11355), a novel lipophilic platinum complex developed to treat hepatocellular carcinoma, is administered into the hepatic artery using an oily lymphographic agent (Lipiodol Ultra-Fluide) as a carrier. We clarified the usefulness of miriplatin as an agent for transarterial chemoembolization.


METHODS
Platinum compounds released from miriplatin into serum, medium and Earle's balanced salt solution were examined. Then, miriplatin and cisplatin were administered to rats bearing hepatoma AH109A tumors in livers. Platinum concentrations in tissues and DNA were assessed.


RESULTS
Miriplatin showed a more sustained release than cisplatin. Dichloro[(1R, 2R)-1, 2-cyclohexane diamine-N, N']platinum, the most abundant platinum compound released from miriplatin, was as effective as cisplatin in inhibiting the growth of cells. Miriplatin was selectively disposed of in tumors, maintained in tumors longer than cisplatin and caused apparent tumor regression inducing platinum-DNA adducts to form and massive apoptosis.


CONCLUSIONS
Miriplatin appears to be a suitable chemotherapeutic agent for transarterial chemoembolization.
Hanada
Mitsuharu
M
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co, Ltd, Osaka, Japan. mitsuharu-hanada@ds-pharma.co.jp
Baba
Akemi
A
Tsutsumishita
Yasuyuki
Y
Noguchi
Toshihiro
T
Yamaoka
Takashi
T
Chiba
Nobuyoshi
N
Nishikaku
Fumio
F
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D002945:Cisplatin / Q000494:pharmacology; D018736:DNA Adducts / Q000378:metabolism; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008220:Lymphography; D008297:Male; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats
D000970:Antineoplastic Agents; D018736:DNA Adducts; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D009944:Organoplatinum Compounds; C406530:miriplatin; D007459:Iodized Oil; D002945:Cisplatin