Jeong Hyeon-Cheol, Kim Min-Gul, Wei Zhuodu, Lee Kyeong-Ryoon, Lee Jaehyeok, Song Im-Sook, Shin Kwang-Hee
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, Korea.
Department of Pharmacology, Medical School, Jeonbuk National University, Jeonju 54907, Korea.
Pharmaceutics. 2022 Jun 18;14(6):1298. doi: 10.3390/pharmaceutics14061298.
A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model for tegoprazan and its major metabolite M1 was developed to predict PK and PD profiles under various scenarios. The PBPK model for tegoprazan and M1 was developed and predicted using the SimCYP simulator and verified using clinical study data obtained after a single administration of tegoprazan. The established PBPK/PD model was used to predict PK profiles after repeated administrations of tegoprazan, postprandial PK profiles, and intragastric pH changes. The predicted tegoprazan and M1 concentration-time profiles fit the observed profiles well. The arithmetic mean ratios (95% confidence intervals) of the predicted to observed values for the area under the curve (AUC), maximum plasma drug concentration (C), and clearance (CL) for tegoprazan and M1 were within a 30% interval. Delayed time of maximum concentration (T) and decreased C were predicted in the postprandial PK profiles compared with the fasted state. This PBPK/PD model may be used to predict PK profiles after repeated tegoprazan administrations and to predict differences in physiological factors in the gastrointestinal tract or changes in gastric acid pH after tegoprazan administration.
建立了替戈拉赞及其主要代谢物M1的基于生理的药代动力学/药效学（PBPK/PD）模型，以预测不同情况下的药代动力学和药效学特征。使用SimCYP模拟器开发并预测了替戈拉赞和M1的PBPK模型，并使用单次给予替戈拉赞后获得的临床研究数据进行了验证。所建立的PBPK/PD模型用于预测替戈拉赞重复给药后的药代动力学特征、餐后药代动力学特征以及胃内pH值变化。预测的替戈拉赞和M1浓度-时间曲线与观察到的曲线拟合良好。替戈拉赞和M1的曲线下面积（AUC）、最大血浆药物浓度（C）和清除率（CL）的预测值与观察值的算术平均比值（95%置信区间）在30%以内。与禁食状态相比，餐后药代动力学特征预测了最大浓度时间（T）延迟和C降低。该PBPK/PD模型可用于预测替戈拉赞重复给药后的药代动力学特征，并预测胃肠道生理因素的差异或替戈拉赞给药后胃酸pH值的变化。
