Pharmacokinetics of mitomycin C in patients after bolus injection and chemobolisation of the hepatic artery with Spherex starch particles

Abstract

The pharmacokinetics of mitomycin C after chemobolisation of the common hepatic artery by micronized Spherex starch particles (mean particle size 30 microns) 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 (co = 743 ng/ml) than without starch particles (co = 987 ng/ml). Accordingly, the AUC values were significantly lower too (AUC = 28.6 micrograms/ml.h with Spherex and 39.7 micrograms/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.

Pharmacokinetics of intra-arterial mitomycin C in the chemoembolization treatment of liver metastases with polyvinylalcohol or degradable starch microspheres

“…The application of MMC in an artery supplying the tumor, combined with an embolization treatment, may have advantages over a systemic treatment given by intravenous application. It was demonstrated [10] that embolization of the common hepatic artery bed vessels by Spherex starch microspheres reduced systemic MMC availability: the AUC was significantly reduced by about 40%, compared to patients treated with an MMC bolus without prior embolization. The initial serum concentration of MMC was also reduced by the embolization procedure (743 ng/ml vs 987 ng/ml), whereas the elimination half-life from the central compartment remained unchanged (27 min vs 28 min).…”

“…It was, moreover, demonstrated that new vascular pathways were opened some minutes after the initial injection. In the studies of Czejka et al [10], showing a reduction of systemic MMC availability, 900 mg of starch particles were used for chemoembolization. The amount of starch microspheres used in the present investigation (600 mg) may have been insufficient for a marked reduction in systemic MMC availability, at least in some of the patients studied.…”

“…[1] [10] [10] [5] The MMC dose was calculated assuming a mean body surface of 1.8 m 2 for an adultIV, intravenous application; IA, intra-arterial application; DSM, degradable starch microspheres; PVA, polyvinylalcohol microspheres UV, ultraviolet detection; ECD, electrochemical detection the group treated with starch microspheres (1472±123; 1448±172; 1670±58 lg min/l standardized on 1 mg MMC). Thus, the systemic toxicity of MMC must be expected to be comparable for both chemoembolization procedures, assuming the MMC dose given is identical.…”