Document Detail

Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct Factor Xa inhibitor.
MedLine Citation:
PMID:  23294275     Owner:  NLM     Status:  MEDLINE    
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.
CONCLUSION: 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.
Dagmar Kubitza; Angelika Roth; Michael Becka; Abir Alatrach; Atef Halabi; Holger Hinrichsen; Wolfgang Mueck
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  76     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-20     Completed Date:  2014-02-03     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  89-98     Citation Subset:  IM    
Copyright Information:
© 2013 Bayer Pharma AG. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.
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MeSH Terms
Administration, Oral
Anticoagulants / adverse effects,  pharmacokinetics*,  pharmacology
Area Under Curve
Case-Control Studies
Factor Xa / antagonists & inhibitors
Hepatic Insufficiency / physiopathology*
Least-Squares Analysis
Metabolic Clearance Rate
Middle Aged
Morpholines / adverse effects,  pharmacokinetics*,  pharmacology
Prothrombin Time
Thiophenes / adverse effects,  pharmacokinetics*,  pharmacology
Reg. No./Substance:
0/Anticoagulants; 0/Morpholines; 0/Polyamines; 0/Thiophenes; 0/rivaroxaban; 182683-00-7/sevelamer; EC Xa
Erratum In:
Br J Clin Pharmacol. 2013 Sep;76(3):489

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