Yoshida M, Kobunai T, Nakano K, Saito H, Toko T, Takeda S, Unemi N
Anticancer and Antimicrobials Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Anticancer Res. 1996 Sep-Oct;16(5A):2869-73.
Menogaril is an antitumor agent active after oral administration, and unlike other anthracyclines, extravasation cannot occur. When the IC90 values of menogaril were plotted versus exposure time on a double-logarithmic scale, the regression lines had slopes between -0.64 and -0.80. These results showed that the mode of action of menogaril was type lb, dependent on the area under the curve (AUC) of concentration versus time, like Adriamycin. In calculations that simulated pharmacokinetic findings if administration were for three consecutive days (the single dose given was 79 mg/kg) or on days 1 and 8 (the single dose was 238 mg/kg), the peak tumor concentration of menogaril was 1870 and 2985 ng/g and the AUC was 68,363 and 89,352 ng/g hour, respectively. Of the dosing schedules tried, these two dosing schedules were the optimum, with satisfactory antitumor activity against mouse solid tumor Colon 26 and with a wide range of effective dose concentrations. Since menogaril was AUC-dependent, it was possible to predict antitumor activity and to choose optimum dosing schedules on the basis of cell-kill kinetic and pharmacokinetic information.
美诺加里尔是一种口服后具有活性的抗肿瘤药物，与其他蒽环类药物不同，它不会发生外渗。当美诺加里尔的IC90值在双对数尺度上与暴露时间作图时，回归线的斜率在-0.64至-0.80之间。这些结果表明，美诺加里尔的作用模式为lb型，与阿霉素一样，取决于浓度对时间曲线下面积（AUC）。在模拟连续三天给药（单次给药剂量为79 mg/kg）或第1天和第8天给药（单次给药剂量为238 mg/kg）的药代动力学结果的计算中，美诺加里尔的肿瘤峰值浓度分别为1870和2985 ng/g，AUC分别为68363和89352 ng/g·小时。在所尝试的给药方案中，这两种给药方案是最优的，对小鼠实体瘤结肠26具有令人满意的抗肿瘤活性，且有效剂量浓度范围较宽。由于美诺加里尔依赖于AUC，因此可以根据细胞杀伤动力学和药代动力学信息预测抗肿瘤活性并选择最佳给药方案。
