Dobbs N A, Twelves C J
ICRF Clinical Oncology Unit, Guy's Hospital, London.
Br J Cancer. 1998 Sep;78(5):662-6. doi: 10.1038/bjc.1998.556.
Doses of cytotoxic drugs are routinely adjusted according to body surface area. We have evaluated this practice in 32 women with advanced breast cancer treated with single-agent epirubicin 12.5-120 mg m(-2). Epirubicin and its metabolites were measured by high-performance liquid chromatography (HPLC). Unadjusted plasma clearance was calculated from dose in mg, and adjusted clearance from dose in mg m(-2). Unadjusted clearance did not correlate with surface area, height, weight, per cent ideal body weight or body mass index. There was no difference in the coefficient of variation (CV) of adjusted and unadjusted clearance (39.4% and 37.7% respectively). The AUC that would have resulted from giving an unadjusted dose was calculated. This predicted AUC was accurate, unbiased and had the same CV as the actual AUC. Similarly, in 11 patients an analysis of actual and predicted neutropenia confirmed that unadjusted dosing would have had no significant effect on the pattern of myelosuppression. Normalization of epirubicin dosage according to surface area appears not to reduce either pharmacokinetic or pharmacodynamic variability.
细胞毒性药物的剂量通常根据体表面积进行调整。我们对32例晚期乳腺癌女性患者进行了评估，这些患者接受单药表柔比星治疗，剂量为12.5 - 120 mg/m²。通过高效液相色谱法（HPLC）测定表柔比星及其代谢产物。未调整的血浆清除率根据毫克剂量计算，调整后的清除率根据毫克/平方米剂量计算。未调整的清除率与体表面积、身高、体重、理想体重百分比或体重指数均无相关性。调整后和未调整清除率的变异系数（CV）没有差异（分别为39.4%和37.7%）。计算了给予未调整剂量时的药时曲线下面积（AUC）。该预测的AUC准确、无偏差，且与实际AUC具有相同的CV。同样，在11例患者中，对实际和预测的中性粒细胞减少进行分析，证实未调整剂量对骨髓抑制模式没有显著影响。根据体表面积对表柔比星剂量进行标准化似乎并不能降低药代动力学或药效学变异性。
