Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct Factor Xa inhibitor.

First published in British Journal of Clinical Pharmacology on 2013 Jul.
Br J Clin Pharmacol. 2013 Jul;76(1):89-98. doi: 10.1111/bcp.12054.

Authors: Kubitza D, Roth A, Becka M, Alatrach A, Halabi A, Hinrichsen H, Mueck W

Abstract

Aim

This study investigated the effects of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban (10 mg), an oral, direct Factor Xa inhibitor.
 

Method

This single centre, non-randomized, non-blinded study included subjects with mild (n = 8) or moderate hepatic impairment (n = 8), according to the Child-Pugh classification, and gender-matched healthy subjects (n = 16).
 

Results

Rivaroxaban was well tolerated irrespective of hepatic function. Mild hepatic impairment did not significantly affect the pharmacokinetics or pharmacodynamics of rivaroxaban, compared with healthy subjects. However, in subjects with moderate hepatic impairment, total body clearance was decreased, leading to a significant increase in the area under the plasma concentration-time curve (AUC). The least-squares (LS)-mean values for AUC were 1.15-fold [90% confidence interval (CI) 0.85, 1.57] and 2.27-fold (90% CI 1.68, 3.07) higher in subjects with mild and moderate hepatic impairment, respectively, than in healthy subjects. Consequently, the pharmacodynamic responses were significantly enhanced in subjects with moderate hepatic impairment. For inhibition of Factor Xa, increases in the area under the effect-time curve and the maximum effect were observed, with LS-mean ratios of 2.59 and 1.24, respectively, vs. healthy subjects. Prolongation of prothrombin time was similar in healthy subjects and those with mild hepatic impairment, but was significantly enhanced in those with moderate hepatic impairment.

Conclusions

Moderate (but not mild) hepatic impairment reduced total body clearance of rivaroxaban after a single 10 mg dose, leading to increased rivaroxaban exposure and pharmacodynamic effects.
 

Read more

Download full article as Pdf file:

Pdf File 1

Pdf File 2

 

REACHING OUT IS EASY AND FAST – LET’S TALK

Prof. Dr. Thomas Forst

Chairman of the Executive Board
located at CRS Mannheim


LET’S TALK SCIENCE
Dr. Marc Hetzel

VP & Head of Business Development
located at CRS Management


LET’S TALK BUSINESS