In vivo properties of the conjugates of mitomycin C with estradiol benzoate and estradiol: pharmacokinetics and antitumor characteristics against P388 leukemia and sarcoma 180.

Abstract

Conjugates of mitomycin C (MMC) with estradiol benzoate and estradiol via glutaric acid, abbreviated to EB-glu-MMC and E-glu-MMC, respectively, as previously reported, were examined concerning their pharmacokinetic behaviors and antitumor effects against two kinds of general and popular tumors, P388 leukemia and Sarcoma 180. EB-glu-MMC and E-glu-MMC were dissolved in propylene glycol. Their solution was administered intraperitoneally to rats and mice in order to examine their plasma concentration-time profiles and antitumor characteristics, respectively. After the administration of EB-glu-MMC, EB-glu-MMC was detected slightly in blood only in the initial stage, while E-glu-MMC and MMC were observed there for a prolonged period. In the administration of E-glu-MMC, a similar phenomenon was observed but the drug retention effect seemed lower than that in EB-glu-MMC. In the antitumor test against P388 leukemia, E-glu-MMC exhibited a better effect than EB-glu-MMC; however, neither conjugate surpassed the effect of MMC. The toxic side effect was improved in each conjugate. As to the growth inhibition against Sarcoma 180, EB-glu-MMC and E-glu-MMC produced good effect and improved the toxic side effect. Especially, in the administration of EB-glu-MMC at the dose of 30 mg eq MMC/kg, a decrease in tumor volume was observed in the latter stage. EB-glu-MMC and E-glu-MMC were demonstrated to produce prolonged retention, to enter the systemic circulation to a fair extent, and to exhibit a good effect against the general solid tumor, Sarcoma 180, in vivo.

• Authors: N Ishiki, H Onishi, Y Machida
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 21 Issue 11 Pg. 1180-6 (Nov 1998) ISSN: 0918-6158 [Print] Japan
• PMID: 9853409 (Publication Type: Journal Article)

Chemical References

• 1a-(4-(3-benzoyloxy-1,3,5(10)-estratrien-17-yloxycarbonyl)butyryl)mitomycin C
• 1a-(4-(3-hydroxy-1,3,5(10)-estratrien-17-yloxycarbonyl)butyryl)mitomycin C
• Antineoplastic Agents
• Mitomycins
• Estradiol
• Mitomycin

Topics

• Animals
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Drug Screening Assays, Antitumor
• Estradiol (analogs & derivatives, pharmacokinetics, therapeutic use)
• Female
• Injections, Intraperitoneal
• Leukemia P388
• Male
• Mice
• Mice, Inbred DBA
• Mitomycin (pharmacokinetics, therapeutic use)
• Mitomycins
• Rats
• Rats, Wistar
• Sarcoma 180