Tsuji Yasuhiro, Iwanaga Nozomi, Mizoguchi Akiko, Sonemoto Emi, Hiraki Yoichi, Ota Yukio, Kasai Hidefumi, Yukawa Eiji, Ueki Yukitaka, To Hideto
Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama.
Biol Pharm Bull. 2015;38(9):1265-71. doi: 10.1248/bpb.b15-00030.
This study describes the population pharmacokinetics and dose personalization of cyclosporine in 36 patients with connective tissue diseases. A one-compartment open model with absorption was adopted as a pharmacokinetic model, and a nonlinear mixed effects model was used to analyze the population pharmacokinetic models. In the final model, age (AGE) and total body weight (TBW) were influential covariates on clearance (CL/F), which was expressed as CL/F (L/h)=17.8×(AGE/60)(-0.269)×(TBW/46.9)(0.408), in addition to the volume of distribution (Vd/F), (L)=98.0 and absorption rate constant (Ka) (h(-1))=0.67 (fixed). The results of the present study provide novel insights into factors involved in determining the most suitable dose and dosing strategy for individual patients with connective tissue disease.
本研究描述了36例结缔组织病患者中环孢素的群体药代动力学及剂量个体化情况。采用具有吸收的单室开放模型作为药代动力学模型，并使用非线性混合效应模型分析群体药代动力学模型。在最终模型中，年龄（AGE）和总体重（TBW）是清除率（CL/F）的影响协变量，清除率表示为CL/F（L/h）=17.8×(AGE/60)(-0.269)×(TBW/46.9)(0.408)，此外，分布容积（Vd/F）为98.0（L），吸收速率常数（Ka）为0.67（固定值，单位：h(-1)）。本研究结果为确定结缔组织病个体患者最合适剂量和给药策略所涉及的因素提供了新的见解。
