Czejka M J, Jäger W, Schüller J
Institute for Pharmaceutical Chemistry, University of Vienna, Austria.
Eur J Drug Metab Pharmacokinet. 1992 Apr-Jun;17(2):85-7. doi: 10.1007/BF03188775.
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.
在5名癌症患者中研究了用微粉化的Spherex淀粉颗粒（平均粒径30微米）对肝总动脉进行化疗栓塞后丝裂霉素C的药代动力学。推注给药并同时阻断动脉导致丝裂霉素C在血管系统中的全身循环显著低于未进行化疗栓塞的推注给药后。血浆浓度-时间曲线显示，在存在Spherex时（co = 743 ng/ml），α期的值低于不存在淀粉颗粒时（co = 987 ng/ml）。因此，AUC值也显著更低（有Spherex时AUC = 28.6微克/毫升·小时，无Spherex时为39.7微克/毫升·小时），从而导致该药物的全身生物利用度更低，肿瘤区域的局部生物利用度更高。两种给药方式下丝裂霉素从中央室的消除情况相似（有Spherex时t1/2 = 27分钟，无Spherex时为28分钟），并显示出该物质的特征性曲线。临床情况显示毒性较轻，副作用有一定程度的减轻。这些结果表明，在患者组织的分布阶段，丝裂霉素C的药代动力学发生了显著且理想的变化。
