In vivo evaluation of mitomycin C-Polylactic acid microcapsules via canine intrahepatic arterial infusion

The therapeutic advantages of a microcapsule dosage form (poly-d, l-lactic acid; 150 ± 25 μm; 5% drug loading) for the intrahepatic arterial delivery of mitomycin C (MMC) were evaluated in dogs on the basis of measurements of the hepatic and peripheral venous concentrations. Hepatic arterial and venous catheters were placed via the femoral in the left lobe of the liver in mongrel dogs. MMC was administered via hepatic arterial catheter at a dose of 0.25 mg/kg in solution with or without embolization and in the microencapsulated form. Pharmacokinetic parameters were obtained from the hepatic and peripheral venous MMC concentrations and novel parameters were developed to permit comparison of the systemic and hepatic exposures to MMC. Ratios of area under the serum concentration-time profiles (AUC), maximum serum concentration (C_max), and mean residence times (MRT) between the hepatic and peripheral veins indicate that embolization with MMC microcapsules results in an up to 2.4-fold reduction in the systemic drug exposure.