Reduction by Norepinephrine of the Side Effects Induced by Combined Hepatic Arterial Administration of Degradable Starch Microspheres and Adriamycin in Rats with a Liver Adenocarcinoma

Abstract

In previous studies we found degradable starch microspheres (DSM) to increase the antitumor effect of adriamycin injected by the hepatic artery in rats with a liver adenocarcinoma. Increased side effects also appeared, namely body weight loss and liver necroses. In the present paper, norepinephrine in four different protocols was added to the injection of adriamycin + DSM to decrease the drug flow to normal tissues. In two protocols norepinephrine decreased the body weight loss. There was also a non-significant decrease in liver necroses but also in antitumor effect. In these experiments we also observed that some rats given adriamycin + DSM got gastric necroses. This was not found when norepinephrine was added. Addition of propranolol to norepinephrine did not decrease side effects. Vasoactive drugs may therefore be of value to diminish adverse side effects of the combination cytostatic agent + DSM, probably decreasing overspill into normal tissues.

Hepatic Intra-Arterial Administration of Doxorubicin and Degradable Starch Microspheres: A pharmacokinetic study in the rat

“…Furthermore, the duration of the vascular occlusion was not monitored, as usually done in the clinical situation but the microspheres were injected in a standardized manner in all animals. Following the standardized rapid injection of microspheres in pharmacological studies using the same DSM dose as in the present study, regional adverse effects, such as GI-toxicity, have been reported (7). Rapidly injecting large amounts of DSM blocks the hepatic artery, forcing the microspheres into the splanchnic circulation where they may temporarily occlude splanchnic organs.…”