Takeuchi H, Okuyama K, Konno O, Jojima Y, Akashi I, Nakamura Y, Iwamoto H, Hama K, Iwahori T, Uchiyama M, Ashizawa T, Matsuno N, Nagao T, Hirano T, Oka K
Department of Pharmaceutics, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.
Transplant Proc. 2005 May;37(4):1745-7. doi: 10.1016/j.transproceed.2005.02.075.
We evaluated the relative clinical potency of cyclosporine (CyA) and tacrolimus (Tac) using pharmacodynamic and pharmacokinetic parameters of the drug to obtain the most suitable converting dose and target trough level. The relative pharmacodynamic potency was examined by the mean ratio of drug concentrations giving 50% inhibition of blastogenesis of lymphocytes (IC50) in 66 chronic renal failure patients. The relative potency estimated from clinical pharmacokinetic parameters was examined by the mean ratio of each pharmacokinetic parameter value of CyA versus Tac. The pharmacokinetic parameters were estimated by 12-hour monitoring of drug blood concentrations in seven CyA patients and seven Tac patients. The mean IC50 ratio of CyA and Tac (CyA/Tac of IC50) was 25.1. The mean area under the concentration-time curve (AUC) ratio (CyA/Tac of AUC) was 25.5, the mean trough level (C(min)) ratio (CyA/Tac of C(min)) was 13.2, and the mean dose per body weight ratio was 25.2. The relative potency estimated from AUC that is the most reliable pharmacokinetic parameter for the estimation of clinical efficacy of calcineurin inhibitors appeared to agree with the relative pharmacodynamic potency estimated from IC50. The data suggest that TAC 25-fold more potent than CyA, which represents a suitable converting dose ratio, and that target trough level of CyA is about 13-fold greater than Tac based on CyA/Tac of C(min). We conclude that these relative values may be useful to estimate the suitable dose and target trough levels to convert between CyA and Tac.
我们利用环孢素（CyA）和他克莫司（Tac）的药效学和药代动力学参数评估了它们的相对临床效力，以获得最合适的转换剂量和目标谷浓度。通过测定66例慢性肾衰竭患者中抑制淋巴细胞增殖50%的药物浓度的平均比值（IC50），来检测相对药效学效力。根据临床药代动力学参数估算的相对效力，通过CyA与Tac各药代动力学参数值的平均比值来检测。通过对7例服用CyA患者和7例服用Tac患者进行12小时的血药浓度监测来估算药代动力学参数。CyA和Tac的平均IC50比值（IC50的CyA/Tac）为25.1。浓度-时间曲线下面积（AUC）的平均比值（AUC的CyA/Tac）为25.5，谷浓度（C(min)）的平均比值（C(min)的CyA/Tac）为13.2，每体重平均剂量比值为25.2。从AUC估算的相对效力（这是估算钙调神经磷酸酶抑制剂临床疗效最可靠的药代动力学参数）似乎与从IC50估算的相对药效学效力一致。数据表明，Tac的效力比CyA高25倍，这代表了合适的转换剂量比，并且基于C(min)的CyA/Tac，CyA的目标谷浓度约比Tac高13倍。我们得出结论，这些相对值可能有助于估算在CyA和Tac之间转换时的合适剂量和目标谷浓度。
