A Pharmacokinetic Drug–Drug Interactions Study between Entecavir and Hydronidone, a Potential Novel Antifibrotic Small Molecule, in Healthy Male Volunteers
A Pharmacokinetic Drug–Drug Interactions Study between Entecavir and Hydronidone, a Potential Novel Antifibrotic Small Molecule, in Healthy Male Volunteers
复制标题
恩替卡韦和氢尼酮（一种潜在的新型抗纤维化小分子）在健康男性志愿者中的药代动力学药物-药物相互作用研究
DOI：
10.1007/s12325-022-02377-x
复制
发表时间：
2022-12
影响因子：
3.8
通讯作者：
Shaojun Shi
中科院分区：
文献类型：
--
作者：
Rui Zhang;Peixia Li;Pengpeng Guo;Jinping Zhou;Jing Wan;Chunxiao Yang;Jiali Zhou;Yani Liu;Shaojun Shi
肝纤维化是肝硬化、恶性肿瘤和肝功能不全的必然过程，而氢化洛酮是一种新型抗肝纤维化药物。本研究旨在研究氢化洛酮与恩替卡韦在中国健康男性受试者体内的药代动力学相互作用。在第1阶段，受试者服用氢洛酮60 mg，q8 h，连续7天。在第2阶段，他们给予恩替卡韦0.5毫克，每天一次，共9天。然后，氢化洛酮和恩替卡韦联合给药6天（第20-26天）。给药后24 h采血，第7、19、26 d采血。结果恩替卡韦与氢化洛酮合用后，其曲线下面积（AUC）0-tss由15.56 ± 2.67增加到16.17 ± 2.77 ng h/ml，而其他药代动力学参数在单药治疗和联合治疗之间具有可比性。与恩替卡韦单药相比，恩替卡韦联合给药后Cmax_ss、AUC 0-t_ss和AUC 0-∞_ss的几何平均值比值（GMR）[90%置信区间（CI）]分别为107.21%（97.04-118.45%）、103.85%（100.94-106.83%）和110.81%（97.19-126.33%）。联合治疗组Cmax，ss、AUC 0-t_ss和AUC 0-∞_ss的GMR和90%CI为102.72%（84.21-125.29%），106.52%结论在健康男性受试者中，盐酸氢洛酮与恩替卡韦无药物相互作用。然而，多剂量的氢洛酮有风险，增加体内恩替卡韦的暴露，这需要进一步澄清。注册号ChiCTR 2200059683（回顾性注册）。
IntroductionHepatic fibrosis is an inevitable process of hepatic sclerosis, malignancy, and insufficiency, and hydronidone is an innovative antifibrosis drug. This study focus on the pharmacokinetic interaction of hydronidone and entecavir in healthy Chinese male subjects.MethodsAn open-label, three-period, multiple-dosage, self-controlled clinical trial was executed in 12 healthy male subjects. In period 1, the subjects took hydronidone 60 mg, q8h, for 7 days. In period 2, they were given entecavir 0.5 mg once daily for 9 days. Then, hydronidone and entecavir were given in combination for 6 days (days 20–26). Blood samples were taken up to 24 h post-dosing, while pre-dose blood samples were drawn on days 7, 19, and 26.ResultsThe area under the curve (AUC)0–t_ssof entecavir slightly increased from 15.56 ± 2.67 to 16.17 ± 2.77 ng h/ml with coadministration with hydronidone, while the other pharmacokinetic parameters of hydronidone and entecavir were comparable between monotherapy and combination therapy. The geometric mean ratios (GMRs) [90% confidence intervals (CIs)] ofCmax_ss,AUC0–t_ss, andAUC0–∞_ssof entecavir after coadministration compared with entecavir alone were 107.21% (97.04–118.45%), 103.85% (100.94–106.83%), and 110.81% (97.19–126.33%), respectively. And the GMRs and 90% CIs ofCmax,ss,AUC0–t_ss, andAUC0–∞_ssfor combination therapy compared with the hydronidone monotherapy group were 102.72% (84.21–125.29%), 106.52% (97.06–116.90%), and 108.86% (96.42–122.89%), respectively.ConclusionsThere was no drug–drug interaction between hydronidone and entecavir in healthy male volunteers. However, multiple doses of hydronidone have a risk with increasing exposure to entecavir in vivo, which needs to be further clarified.Registration numberChiCTR2200059683 (retrospectively registered).
登录
查看更多内容
OAT1和OAT3：恩替卡韦和JBP485之间药物相互作用的靶点
影响因子：
4.6
作者：
Xu, Qinghan;Wang, Changyuan;Liu, Kexin
通讯作者：
Liu, Kexin
影响因子：
6.7
作者：
Bin-Qiao Wang;Yong-Lin Wang;Ke-Qing Shi
通讯作者：
Bin-Qiao Wang;Yong-Lin Wang;Ke-Qing Shi
影响因子：
24.3
作者：
罗太阳;刘小慧;汤日波;董建增;戴天医;谷孝艳;何怡华
通讯作者：
罗太阳;刘小慧;汤日波;董建增;戴天医;谷孝艳;何怡华
肝纤维化：治疗靶点和药物治疗进展
影响因子：
5.5
作者：
Tan Z;Sun H;Xue T;Gan C;Liu H;Xie Y;Yao Y;Ye T
通讯作者：
Ye T
影响因子：
3.6
作者：
Guo YC;Lu LG
通讯作者：
Lu LG