Pharmacokinetics of Intraarterial Mitomycin C in Humans1

The pharmacological advantage of mitomycin C (MMC) given by intraarterial infusion as compared to i.v. infusion was studied in seven patients with cancer metastatic to the liver. Hepatic artery, hepatic vein, and peripheral vein catheters were placed, and then each patient received constant infusions of MMC via the intraarterial and peripheral i.v. routes at 0.4,1.2, and 4.0 mg/ sq m/hr. MMC concentrations were measured in the hepatic artery, hepatic vein, and a peripheral vein by high-pressure liquid chromatography after steady state had been reached at 2 hr. Mean plasma clearance increased significantly with infusion rate from 0.6 liter/min at 0.4 mg/sq m/hr to 1.1 liters/min at 4.0 mg/ sq m/hr. The calculated relative advantage of treating hepatic tumors via the intraarterial route (R,) was found to be 2.5to 3.6fold at a plasma flow rate of 0.4 liter/sq m and MMC infusion rates of 0.4 to 4.0 mg/sq m/hr. The hepatic vein MMC concen tration averaged 30% higher during intraarterial than during i.v. infusion. Hepatic extraction of MMC averaged only 23%, so that the intraarterial route offered little advantage with respect to reduced systemic toxicity. These data suggest a limited phar macological rationale for the selection of the intraarterial route for the treatment of hepatic tumors with MMC.