Kearns C M, Belani C P, Erkmen K, Zuhowski M, Hiponia D, Zacharski D, Engstrom C, Ramanathan R, Trenn M R, Aisner J
Division of Developmental Therapeutics, University of Maryland Cancer Center, Baltimore 21201, USA.
Semin Oncol. 1995 Oct;22(5 Suppl 12):1-4; discussion 5-7.
We studied the pharmacokinetics of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin administered in combination to 21 patients with advanced non-small cell lung cancer. Paclitaxel was administered as a 24-hour intravenous infusion at doses of 135 to 200 mg/m2. Carboplatin, dosed to a target area under the concentration-time curve of 5, 7, 9, or 11 mg/mL.min, was administered as a 20-minute infusion immediately following paclitaxel. Neither the paclitaxel concentrations at the end of the infusion nor the terminal elimination of paclitaxel, as assessed by the duration of time that plasma paclitaxel concentrations were 0.05 mumol/L or greater, were different compared with historical data of paclitaxel as a single agent. Thus, we concluded that carboplatin had no perceived effect on the pharmacokinetics of paclitaxel in this schedule. The observed areas under the concentration-time curves for carboplatin were consistently 10% to 15% less than the target values. Although this may indicate a possible interaction between paclitaxel and carboplatin, it also may have been a result of inadequate assessment of glomerular filtration rate, which was used to determine the carboplatin dose.
我们研究了将紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）与卡铂联合应用于21例晚期非小细胞肺癌患者的药代动力学。紫杉醇以135至200mg/m²的剂量进行24小时静脉输注。卡铂的给药目标是使浓度-时间曲线下面积达到5、7、9或11mg/mL·min，在紫杉醇输注结束后立即进行20分钟输注。无论是输注结束时的紫杉醇浓度，还是通过血浆紫杉醇浓度≥0.05μmol/L的持续时间评估的紫杉醇终末消除情况，与紫杉醇单药治疗的历史数据相比均无差异。因此，我们得出结论，在该给药方案中卡铂对紫杉醇的药代动力学没有明显影响。观察到的卡铂浓度-时间曲线下面积始终比目标值低10%至15%。虽然这可能表明紫杉醇与卡铂之间存在潜在相互作用，但也可能是由于用于确定卡铂剂量的肾小球滤过率评估不足所致。
