Virtual population pharmacokinetic using physiologically based pharmacokinetic model for evaluating bioequivalence of oral lacidipine formulations in dogs

作     者：Bin Yang Chunnuan Wu Bin Ji Mingrui Wu Zhonggui He Lei Shang Jin Sun 

作者机构：Department of PharmaceuticsSchool of PharmacyShenyang Pharmaceutical UniversityShenyangChina Department of PharmacyTianjin Medical University Cancer Institute and HospitalTianjinChina Department of Pharmaceutical analysisSchool of PharmacyShenyang Pharmaceutical UniversityShenyangChina School of PharmacyChina Medical UniversityShenyangChina Municipal Key Laboratory of BiopharmaceuticsSchool of PharmacyShenyang Pharmaceutical UniversityShenyangChina 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2017年第12卷第1期

页      面：98-104页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：the National Natural Science Foundation of China (No. 81173009) the Technology Bureau in Shenyang (No. ZCJJ2013402) the Project for New Century Excellent Talents of Ministry of Education (No. NCET-12-1015) 

主　　题：Physiologically based pharmacokinetic model Virtual population pharmacokinetic Bioequivalence Lacidipine Amorphous solid dispersions 

摘      要：The aim of the present study was to investigate virtual population pharmacokinetic using physiologically based pharmacokinetic(PBPK) model for evaluating bioequivalence of oral lacidipine formulations in dogs. The dissolution behaviors of three lacidipine formulations including one commercial product and two self-made amorphous solid dispersions(ASDs)capsules were determined in 0.07% Tween 80 media. A randomized 3-period crossover design in 6 healthy beagle dogs after oral administration of the three formulations at a single dose of 4 mg was conducted. The PBPK modeling was utilized for the virtual bioequivalence study.In vitro dissolution experiment showed that the dissolution behaviors of lacidipine amorphous solid dispersions(ASDs) capsules, which was respectively prepared by HPMC-E5 or Soluplus, as polymer displayed similar curves compared with the reference formulation in 0.07% Tween 80 media. In vivo pharmacokinetics experiments showed that three formulations had comparable maximum plasma drug concentration(Cmax), and the time(Tmax) to reach Cmax of lacidipine tablet, which was prepared by Soluplus, as polymer was slower than other two formulations in consistency with the in vitro dissolution rate. The 90% confidence interval(CI) for the Cmax, AUC0–24 h and AUC0–∞ of the ratio of the test drug to the reference drug exceeded the acceptable bioequivalence(BE) limits(0.80–1.25). However, the 90% CI of the AUC0–24 h, AUC0–∞ and Cmax of the ratio of test to reference drug were within the BE limit,calculated using PBPK modeling when the virtual subjects reached 24 dogs. The results all demonstrated that virtual bioequivalence study can overcome the inequivalence caused by inter-subject variability of the 6 beagle dogs involved in in vivo experiments.