Tecarfarin

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Tecarfarin
Tecarfarin skeletal.svg
Clinical data
Other namesATI-5923
Routes of
administration
By mouth
ATC code
  • None
Legal status
Legal status
  • Investigational
Pharmacokinetic data
Elimination half-life87–136 hours[1]
Identifiers
  • 1,1,1,3,3,3-Hexafluoro-2-methyl-2-propanyl 4-[(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]benzoate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H14F6O5
Molar mass460.328 g·mol−1
3D model (JSmol)
  • CC(C(F)(F)F)(C(F)(F)F)OC(=O)c1ccc(cc1)Cc2c(c3ccccc3oc2=O)O
  • InChI=1S/C21H14F6O5/c1-19(20(22,23)24,21(25,26)27)32-17(29)12-8-6-11(7-9-12)10-14-16(28)13-4-2-3-5-15(13)31-18(14)30/h2-9,28H,10H2,1H3
  • Key:QFLNTQDOVCLQKW-UHFFFAOYSA-N

Tecarfarin is a vitamin K antagonist under development for use as an anticoagulant.[2] A Phase II/III clinical trial in 607 people, comparing it to the established vitamin K antagonist warfarin, found no difference in quality of anticoagulation or side effects between the two drugs in the overall population.[3] Among patients taking CYP2C9 interacting drugs however, the tecarfarin patients’ TTR was 72.2% (n=92) vs 69.9% (n=87) for warfarin patients (pint=0.16); among patients who had both a CYP2C9 variant allele and taking a CYP2C9 interacting drug, TTR was 76.5% and 69.5% for the tecarfarin (n=24) and warfarin (n=31) groups, respectively (pint=0.24). This study included in 84 (14%) patients with a mechanical heart valve as an indication for anticoagulation therapy. No thrombotic or embolic events were observed in the tecarfarin treated subjects. In contrast to warfarin, tecarfarin is not affected by the cytochrome P450 inhibiting drug fluconazole,[4] indicating a lower potential for interactions with other drugs.[2]

A randomized, pharmacokinetic study in which healthy volunteer subjects and patients with severe chronic kidney disease received single-dose warfarin or tecarfarin in a crossover design was performed. This showed that mean plasma concentrations of (S)-warfarin and (R,S)-warfarin were higher (44 and 27%, respectively) in the subjects with CKD than in the healthy subjects. Both of these values fell outside of the 90% confidence interval of equivalence. For tecarfarin, the difference was less than 15% higher. Elimination half-life (t1/2) increased by 20% for (S)-warfarin and by 8% for (R,S)-warfarin and decreased by 8% for tecarfarin.[5] A Phase III trial with 1000 people fully enriched with patients known to have at least two factors reducing CYP2C9 function, also comparing tecarfarin to warfarin, is planned.[6]

References[edit]

  1. ^ Albrecht D, Ellis D, Canafax DM, Combs D, Druzgala P, Milner PG, Midei MG (April 2017). "Pharmacokinetics and pharmacodynamics of tecarfarin, a novel vitamin K antagonist oral anticoagulant". Thrombosis and Haemostasis. 117 (4): 706–717. doi:10.1160/TH16-08-0623. PMID 28180234.
  2. ^ a b Spreitzer H (27 February 2017). "Neue Wirkstoffe – Tecarfarin". Österreichische Apothekerzeitung (in German) (5/2017).
  3. ^ Whitlock RP, Fordyce CB, Midei MG, Ellis D, Garcia D, Weitz JI, et al. (August 2016). "A randomised, double blind comparison of tecarfarin, a novel vitamin K antagonist, with warfarin. The EmbraceAC Trial". Thrombosis and Haemostasis. 116 (2): 241–50. doi:10.1160/TH15-11-0910. PMID 27173100.
  4. ^ Bavisotto LM, Ellis DJ, Milner PG, Combs DL, Irwin I, Canafax DM (April 2011). "Tecarfarin, a novel vitamin K reductase antagonist, is not affected by CYP2C9 and CYP3A4 inhibition following concomitant administration of fluconazole in healthy participants". Journal of Clinical Pharmacology. 51 (4): 561–74. doi:10.1177/0091270010370588. PMID 20622200. S2CID 36344392.
  5. ^ Albrecht D, Turakhia MP, Ries D, Marbury T, Smith W, Dillon D, et al. (November 2017). "Pharmacokinetics of Tecarfarin and Warfarin in Patients with Severe Chronic Kidney Disease". Thrombosis and Haemostasis. 117 (11): 2026–2033. doi:10.1160/th16-10-0815. PMID 28933798.
  6. ^ Clinical trial number NCT02522221 for "Tecarfarin Anti-Coagulation Trial (TACT)" at ClinicalTrials.gov.