The pharmacology of novel oral anticoagulants

被引:48
作者
DeWald, Tracy A. [1 ,2 ,3 ]
Becker, Richard C. [1 ,2 ]
机构
[1] Duke Univ, Med Ctr, Duke Clin Res Inst RCB, Div Clin Pharmacol TAD, Durham, NC USA
[2] Duke Univ, Med Ctr, Duke Clin Res Inst RCB, Div Cardiovasc Med RCB, Durham, NC USA
[3] DUMC, Duke Heart Ctr, Durham, NC 27710 USA
关键词
Dabigatran; Apixaban; Rivaroxaban; Edoxaban; Pharmacokinetics; Membrane transporters; DIRECT THROMBIN INHIBITOR; FACTOR XA INHIBITOR; MULTIDRUG-RESISTANCE PROTEINS; P-GLYCOPROTEIN; DABIGATRAN ETEXILATE; DRUG ABSORPTION; ATRIAL-FIBRILLATION; TISSUE DISTRIBUTION; CYTOCHROME-P450; 3A; TRANSPORT PROTEINS;
D O I
10.1007/s11239-013-0967-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Anticoagulation for the prevention of stroke is an important aspect of the management of atrial fibrillation. Novel anticoagulants including oral factor Xa inhibitors rivaroxaban and apixaban and the direct thrombin inhibitor dabigatran have emerged as important therapeutic treatment options for prevention of stroke in non-valvular atrial fibrillation. These agents offer practical advantages over traditional vitamin K antagonists, however an understanding of their individual pharmacokinetic and other agent-specific differences is essential for identifying appropriate candidates for therapy, and for selecting the appropriate agent that will be effective and safe. Here, we review the pharmacokinetic process of oral medication use, summarize the newer anticoagulants, their pharmacology, individual pharmacokinetic features, and explore possible explanations for the differences in bleeding outcomes observed in the clinical trials.
引用
收藏
页码:217 / 233
页数:17
相关论文
共 113 条
[1]   Differential propensity for major hemorrhagic events in patients with different types of arterial disease [J].
Achterberg, S. ;
Visseren, F. L. J. ;
Kappelle, L. J. ;
Pruissen, D. M. O. ;
Van der Graaf, Y. ;
Algra, A. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2011, 9 (09) :1724-1729
[2]   Patients with coronary, cerebrovascular or peripheral arterial obstructive disease differ in risk for new vascular events and mortality: the SMART study [J].
Achterberg, Sefanja ;
Cramer, Maarten J. M. ;
Kappelle, L. Jaap ;
de Borst, Gert Jan ;
Visseren, Frank L. J. ;
van der Graaf, Yolanda ;
Algra, Ale .
EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION, 2010, 17 (04) :424-430
[3]   Inhibition of Factor Xa: A potential target for the development of new anticoagulants [J].
Alexander J.H. ;
Singh K.P. .
American Journal of Cardiovascular Drugs, 2005, 5 (5) :279-290
[4]   Characterization of the human ABC superfamily: Isolation and mapping of 21 new genes using the expressed sequence tags database [J].
Allikmets, R ;
Gerrard, B ;
Hutchinson, A ;
Dean, M .
HUMAN MOLECULAR GENETICS, 1996, 5 (10) :1649-1655
[5]  
[Anonymous], 2010, Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications
[6]  
[Anonymous], AAPS J
[7]  
[Anonymous], CHEST, DOI 10.1378/chest.1388403
[8]   CORRELATION BETWEEN ORAL-DRUG ABSORPTION IN HUMANS AND APPARENT DRUG PERMEABILITY COEFFICIENTS IN HUMAN INTESTINAL EPITHELIAL (CACO-2) CELLS [J].
ARTURSSON, P ;
KARLSSON, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 175 (03) :880-885
[9]   Role of transport proteins in drug absorption, distribution and excretion [J].
Ayrton, A ;
Morgan, P .
XENOBIOTICA, 2001, 31 (8-9) :469-497
[10]   Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir [J].
Balimane, PV ;
Tamai, I ;
Guo, AL ;
Nakanishi, T ;
Kitada, H ;
Leibach, FH ;
Tsuji, A ;
Sinko, PJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 250 (02) :246-251