A Pharmacokinetic Drug-Drug Interactions Study between Entecavir and Hydronidone, a Potential Novel Antifibrotic Small Molecule, in Healthy Male Volunteers.

Abstract

Hepatic 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. An open-label, three-period, multiple-dosage, self-controlled clinical trial was executed in 12 healthy male subjects. In period 1, the subjects took hydronidone 60mg, q8h, for 7days. In period 2, they were given entecavir 0.5mg once daily for 9days. Then, hydronidone and entecavir were given in combination for 6days (days 20-26). Blood samples were taken up to 24h post-dosing, while pre-dose blood samples were drawn on days 7, 19, and 26. The area under the curve (AUC)0-t_ss of entecavir slightly increased from 15.56 ± 2.67 to 16.17 ± 2.77ngh/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)] of Cmax_ss, AUC0-t_ss, and AUC0-∞_ss of 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 of Cmax,ss, AUC0-t_ss, and AUC0-∞_ss for 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. There 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. ChiCTR2200059683 (retrospectively registered).