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Pharmacokinetics and Pharmacodynamics
PKP-003 Genetic polymorphisms associated with the dose of acenocoumarol
  1. C García Fernandez,
  2. C Gomez Peña,
  3. CL Dávila Fajardo,
  4. A Caballero Romero,
  5. S Ruiz Fuentes,
  6. S Belda Rustarazo,
  7. C Medarde Caballero,
  8. C Fernandez Lopez,
  9. R Moron Romero,
  10. J Cabeza Barrera
  1. Hospital San Cecilio, Farmacia Hospitalaria, Granada, Spain

Abstract

Background The coumarins have a narrow therapeutic window and there is wide inter- and intra-individual variability in dose requirements. Therefore, patients are monitored by measuring the international normalised ratio (INR). Recent discoveries show relationship between genetic polymorphisms and dose requirements of coumarins. Genetic polymorphisms affect CYP2C9*2(*2/*2), CYP2C9*3 (*1/*3, *3/*3) and VKORC1 (CT, TT) reduce the enzyme activity, so a lower dose of anticoagulant drug may be required. At the same time, genetic polymorphism in CYPF2 (TT), decreases the enzyme activity; in this case the patient may need higher doses of anticoagulant.

Purpose To determine the percentage of potential patients whose dose may need to change taking into account the prevalence of polymorphisms CYP2C9*2 (*2/*2), CYP2C9*3 (*1/*3, *3/*3), VKORC1 (CT, TT) and CYP4F2 (TT) in patients with thromboembolic disease, atrial fibrillation and mechanical heart valve prostheses.

Materials and methods This was an observational, descriptive, transversal study with 344 patients treated with acenocoumarol, from May 2012 to May 2013. Saliva samples were taken from all the patients. For genotyping we used TaqMan probes and allelic discrimination technique. We performed a univariate descriptive analysis of the frequencies of genetic polymorphisms affecting the doses (CYP2C9 * 2, CYP2C9*3, VKORC1, CYP4F2). We focused on the polymorphisms that affect the drug dose (CYP2C9*2 (*2/*2), CYP2C9*3 (*1/*3, *3/*3), VKORC1 (CT, TT) and CYP4F2 (TT).

Results Genotypes distribution: CYP2C9*2 (*2/*2): 2.3% patients, CYP2C9*3 (*1/*3): 16.3% and (*3/*3): 1.4% patients. VKORC1 CT: 49.4% and VKORC1 TT: 13.1% and the CYP4F2 TT: 15.1%.

The overall percentage of patients who might need a change in the dose is 75.87% according to the pharmacogenetic guides.

Conclusions Due to the high percentage of patients who may potentially need a change in dose, it is necessary to start genotyping patients on acenocoumarol in order to keep them controlled.

No conflict of interest.

https://doi.org/10.1136/ejhpharm-2013-000436.338

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