Ekhart Corine, Rodenhuis Sjoerd, Schellens Jan H M, Beijnen Jos H, Huitema Alwin D R
Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Cancer Chemother Pharmacol. 2009 Jun;64(1):115-22. doi: 10.1007/s00280-008-0856-x. Epub 2008 Nov 7.
The purpose of this study was to determine the potential utility of alternative weight descriptors in the Cockcroft-Gault equation to more accurately predict carboplatin clearance in underweight, normal weight, overweight and obese patients.
Clearance values obtained from individual fits using NONMEM were compared to predicted carboplatin clearances calculated using the modified Calvert formula in which creatinine clearance was calculated with the Cockcroft-Gault equation using diverse weight descriptors.
This study indicated that lean body mass was the best weight descriptor in underweight and normal weight patients, while adjusted ideal body weight was the best weight descriptor in overweight and obese patients. However, a flat dose based on the population carboplatin clearance performed better in all weight categories than the use of the Cockcroft-Gault equation with diverse weight descriptors.
These results suggest that in overweight and obese patients, with a normal renal function, a flat carboplatin dose should be administered, based on the population carboplatin clearance (8.38 l/h = 140 mL/min). Thus, in case an AUC of 5 mg min/mL is desired, the appropriate dose for carboplatin would be 5 x 140 = 700 mg.
本研究的目的是确定Cockcroft-Gault方程中替代体重描述符的潜在效用，以更准确地预测体重过轻、正常体重、超重和肥胖患者的卡铂清除率。
将使用NONMEM从个体拟合中获得的清除率值与使用改良的Calvert公式计算的预测卡铂清除率进行比较，其中肌酐清除率使用Cockcroft-Gault方程并采用不同的体重描述符进行计算。
本研究表明，瘦体重是体重过轻和正常体重患者中最佳的体重描述符，而调整后的理想体重是超重和肥胖患者中最佳的体重描述符。然而，基于群体卡铂清除率的固定剂量在所有体重类别中比使用具有不同体重描述符的Cockcroft-Gault方程表现更好。
这些结果表明，对于超重和肥胖且肾功能正常的患者，应根据群体卡铂清除率（8.38升/小时 = 140毫升/分钟）给予固定的卡铂剂量。因此，如果期望达到5毫克·分钟/毫升的AUC，卡铂的合适剂量应为5×140 = 700毫克。
