PBPK Modeling of Coproporphyrin I as an Endogenous Biomarker for Drug Interactions Involving Inhibition of Hepatic OATP1B1 and OATP1B3.
PBPK Modeling of Coproporphyrin I as an Endogenous Biomarker for Drug Interactions Involving Inhibition of Hepatic OATP1B1 and OATP1B3.
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DOI：
10.1002/psp4.12348
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Sugiyama Y
中科院分区：
文献类型：
--
作者：
Yoshikado T;Toshimoto K;Maeda K;Kusuhara H;Kimoto E;Rodrigues AD;Chiba K;Sugiyama Y
本研究的目的是使用OATP 1B抑制剂利福平（300和600 mg，口服）的临床DDI数据，建立粪卟啉I（CP-I）的生理学药代动力学（PBPK）模型，CP-I是一种支持预测涉及肝有机阴离子转运多肽1B（OATP 1B）的药物相互作用（DDI）的生物标志物。根据既往报告，用作OATP 1Bs（Ki、u、OATP 1Bs）和多药耐药相关蛋白2介导胆汁排泄的初始输入参数的利福平体内抑制常数估计分别为0.23和0.87 μM。敏感性分析表明，Ki，u，OATP 1Bs和CP‐I的生物合成速率影响相互作用的大小。通过非线性最小二乘拟合优化的Ki，u，OATP 1Bs值约为初始值的0.5倍。确定使用校正的个体Ki，u，OATP 1B值（体外Ki，u（他汀类药物）/体外Ki，u（CP-I）比值）可良好预测四种他汀类药物的血药浓度-时间曲线。总之，CP-I的PBPK建模支持OATP 1B介导DDI的动态预测。
The aim of the present study was to establish a physiologically based pharmacokinetic (PBPK) model for coproporphyrin I (CP‐I), a biomarker supporting the prediction of drug‐drug interactions (DDIs) involving hepatic organic anion transporting polypeptide 1B (OATP1B), using clinical DDI data with an OATP1B inhibitor rifampicin (300 and 600 mg, orally). The in vivo inhibition constants of rifampicin used as initial input parameters for OATP1Bs (K i,u,OATP1Bs) and multidrug resistance‐associated protein two‐mediated biliary excretion were estimated as 0.23 and 0.87 μM, respectively, from previous reports. Sensitivity analysis demonstrated that the K i,u,OATP1Bs and biosynthesis rate of CP‐I affected the magnitude of the interaction. K i,u,OATP1Bs values optimized by nonlinear least‐squares fitting were ~0.5‐fold of the initial value. It was determined that the blood concentration‐time profiles of four statins were well‐predicted using corrected individual K i,u,OATP1B values (ratio of in vitro K i,u(statin)/in vitro K i,u(CP‐I)). In conclusion, PBPK modeling of CP‐I supports dynamic prediction of OATP1B‐mediated DDIs.
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影响因子：
2.1
作者：
Watanabe, Masaki;Watanabe, Takao;Tamai, Ikumi
通讯作者：
Tamai, Ikumi
影响因子：
6.7
作者：
Barnett, Shelby;Ogungbenro, Kayode;Galetin, Aleksandra
通讯作者：
Galetin, Aleksandra
影响因子：
6.7
作者：
Elsby, R.;Hilgendorf, C.;Fenner, K.
通讯作者：
Fenner, K.
DOI：
10.1124/jpet.110.170092
发表时间：
2010-11-01
影响因子：
3.5
作者：
Takashima, Tadayuki;Nagata, Hiroko;Watanabe, Yasuyoshi
通讯作者：
Watanabe, Yasuyoshi
影响因子：
6.7
作者：
Yang, K.;Battista, C.;Howell, B. A.
通讯作者：
Howell, B. A.