Comparison of efficacy, toxicity and pharmacokinetics of free adriamycin and adriamycin linked to oxidized dextran in rats.
Adriamycin linked to oxidized dextran (ADM-OXD) via Schiff's base formation was compared with free adriamycin with regard to antitumor activity, acute toxicity and plasma pharmacokinetics in rats following i.v. administration. ADM-OXD showed higher activity against Walker carcinosarcoma 256 than free adriamycin. On the other hand, the acute toxicity of ADM-OXD was about three times less than that of free adriamycin. In contrast to free adriamycin, a very high plasma level of adriamycin was found after i.v. administration of ADM-OXD. The area under the plasma concentration curve with ADM-OXD was about 160-fold higher than with free adriamycin. Thus, the improvement of the therapeutic index in the case of ADM-OXD might be due to the difference in the disposition of ADM-OXD and free adriamycin in rats.
Ueda
Y
Y
Munechika
K
K
Kikukawa
A
A
Kanoh
Y
Y
Yamanouchi
K
K
Yokoyama
K
K
D000818:Animals; D002279:Carcinoma 256, Walker / Q000188:drug therapy; D003911:Dextrans; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D004337:Drug Carriers; D051381:Rats
D003911:Dextrans; D004337:Drug Carriers; D004317:Doxorubicin