Twenty patients with solid tumors received 30 mg/M2 of adriamycin. Various tissue samples were intraoperatively obtained from 18 patients, about 1.5-5 hours after an intravenous (IV) bolus dose. Normal liver showed the highest levels of adriamycin uptake (2.3-19.8 &g); lymph nodes were second; muscle and bone marrow, next; fat and skin had the lowest adriamycin uptake (0.04-0.40 pglg). Tumor tissue, excluding that with much necrosis and hemorrhaging, had adriamycin concentrations which approximated those of the liver (1.1-9.2 &g). Six patients, all with hepatic malignancies, had prolonged plasma concentration studies after IV administration; 5 also had adriamycin administered directly into the hepatic artery catheter. Adriamycin-plasma-time courses were similar, whether the drug was administered by bolus directly into the hepatic artery or peripheral vein. The concentration of metabolites after hepatic intraarterial administration was definitely higher than that after IV administration. Patients with hepatic dysfunction had delayed plasma clearance and secondarily elevated levels approximately 160 and 300 minutes after administration.
Cancer 45:2231-2239, 1980.
HE CONCENTRATION-TIME COURSE of adriamycin,
T and quite possibly its metabolites, in plasma, and in normal and tumor tissue is important in regard to its therapeutic outcome and toxic side-effects. Initial pharmacologic studiess and early clinical e x p e r i e n ~e ~, ~ suggested that the drug should be administered by means of intermittent single intravenous (IV) bolus dose. However, it was hypothesized that adriamycin given intraarterially (IA) might maximize local tumor destructian and minimize systemic toxicity." A variety of reasons suggest that adriamycin may be an ideal agent for IA use in selected tumors. First, there is evidence that in humans, metabolism may not be necessary in order β¬or it to have an antitumor effect. Second, adriamycin binds avidly to and causes visible damage to D N A z 4 This avidity for DNA, which occurs rapidly in vitro, suggests that even a single IA transit would result in substantial binding of the drug to DNA of tumor tissues. We have administered adriamycin directly into the hepatic artery in order to treat hepatic m a l i g n a n c i e ~. ~~ Thus, we have determined if significant differences in the plasma levels exist between IA and IV administration of adriamycin.