In:
British Journal of Haematology, Wiley, Vol. 167, No. 4 ( 2014-11), p. 547-553
Kurzfassung:
Interindividual variations in dose requirements of oral vitamin K antagonists ( VKA ) are attributed to several factors, including genetic variant alleles of vitamin K epoxide reductase complex subunit 1 ( VKORC 1) and cytochrome P450 2C9 ( CYP 2C9), but also interaction with co‐medications. In this context, proton pump inhibitor ( PPI )‐related alterations of VKA maintenance dose requirements have been published. The present investigation aimed to test for an interaction profile of oral VKA ‐therapy and PPI s in relation to the CYP 2C9 genotype. Median weekly stable VKA dose requirements over 1 year were recorded in 69 patients. Patients were genotyped for CYP 2C9 *2, CYP 2C9 *3, VKORC 1 c.‐1639G 〉 A and VKORC 1 c.174‐136C 〉 T and assessed for an association with PPI use and total VKA maintenance dose requirements. PPI users with CYP 2C9 genetic variations required significantly lower weekly VKA maintenance doses than those with the wild‐type genotype ( t ‐test: P = 0·02). In contrast, in subjects without PPI use, the CYP 2C9 genotype had no significant influence on oral VKA dose requirements. Further, the combined CYP 2C9 / VKORC 1 genotype was a significant predictor for VKA dose requirements [linear regression: estimate: −1·47, standard error: 0·58 ( P = 0·01)]. In conclusion, in carriers of CYP 2C9 gene variations, the interference with the VKA metabolism is modified by PPI co‐medication and the VCKORC 1 genotype. Preceding knowledge of the genetic profile and the awareness for potentially occurring severe over‐anticoagulation problems under PPI co‐medication could contribute to a safer and personalized VKA pharmacotherapy.
Materialart:
Online-Ressource
ISSN:
0007-1048
,
1365-2141
DOI:
10.1111/bjh.2014.167.issue-4
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2014
ZDB Id:
1475751-5