PHARMACOKINETICS OF MITOMYCIN-C IN PATIENTS AFTER BOLUS INJECTION AND CHEMOBOLISATION OF THE HEPATIC-ARTERY WITH SPHEREX STARCH PARTICLES

The Pharmacokinetics of mitomycin C after chemobolisation of the common hepatic artery by micronized Spherex starch particles (mean particle size 30-mu-m) were investigated in 5 cancer patients. Bolus injection and simultaneous occlusion of the artery lead to a significantly lower systemic circulation of mitomycin C in the blood vessel system than after bolus injection without chemobolisation. The plasma concentration-time curves showed lower values in the alpha-phase in the presence of Spherex (c(o) = 743 ng/ml) than without starch particles (c(o) = 987 ng/ml). Accordingly, the AUC values were significantly lower too (AUC = 28.6-mu-g/ml.h with Spherex and 39.7-mu-g/ml.h without Spherex), thus leading to a lower systemic bioavailability of the drug and a higher local bioavailability in the tumor region. Elimination of mitomycin from the central compartment was similar for both administrations (t1/2 = 27 min with Spherex and 28 min without Spherex) and showed the characteristic profile of the substance. The clinical picture showed a milder toxicity with a certain loss of side effects. These results indicate a significant and desirable change in the pharmacokinetics of mitomycin C during the distribution phase into the tissue of patients.