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International Journal of Clinical Pharmacy

, Volume 34, Issue 6, pp 837–844 | Cite as

Validation of pharmacogenetic algorithms and warfarin dosing table in Egyptian patients

  • Naglaa Samir BazanEmail author
  • Nirmeen Ahmed Sabry
  • Amal Rizk
  • Sherif Mokhtar
  • Osama Badary
Research Article

Abstract

Background Warfarin remains a difficult drug to use due to the large variability in dose response. Clear understanding of the accuracy of warfarin pharmacogenetic dosing methods might lead to appropriate control of anticoagulation. Objective This study aims to evaluate the accuracy of warfarin dosing table and two pharmacogenetic algorithms, namely the algorithms of Gage et al. (Clin Pharmacol Ther 84:326–331, 2008), and the International Warfarin Pharmacogenetics Consortium algorithm (IWPC) in a real Egyptian clinical setting. Additionally, three non-pharmacogenetic dosing methods (the Gage, IWPC clinical algorithms and the empiric 5 mg/day dosing) were evaluated. Setting Sixty-three Egyptian patients on a stable therapeutic warfarin dose were included. Patients were recruited from the outpatient clinic of the critical care medicine department. Methods CYP2C9 and VKORC1 polymorphisms were genotyped by real time PCR system. Predicted doses by all dosing methods were calculated and compared with the actual therapeutic warfarin doses. Results The Gage algorithm (adjusted R2 = 0.421, and mean absolute error (MAE) = 3.3), and IWPC algorithm (adjusted R2 = 0.419, MAE = 3.2) produced better accuracy than did the warfarin dosing table (adjusted R2 = 0.246, MAE = 3.5), the two clinical algorithms (R2 = 0.24, MAE = 3.7) and the fixed dose approach (MAE = 3.9). However, all dosing models produced comparable clinical accuracy with respect to proportion of patients within 1 mg/day of actual dose (ideal dose). Non-pharmacogenetic methods severely over-predicted dose (defined as ≥2 mg/day more than actual dose) compared to the three pharmacogenetic models. In comparison to non-pharmacogenetic methods, the three pharmacogenetic models performed better regarding the low dose group in terms of percentage of patients within ideal dose. In the high dose group, none of the dosing models predicted warfarin doses within ideal dose. Conclusion Our study showed that genotype-based dosing improved prediction of warfarin therapeutic dose beyond that available with the fixed-dose approach or the clinical algorithms, especially in the low-dose group. However, the two pharmacogenetic algorithms were the most accurate.

Keywords

CYP2C9 Dosage Dosing algorithms Dosing table Egypt Pharmacogenetics VKORC1 Warfarin 

Notes

Acknowledgments

We express our deep appreciation and thankfulness to the Critical Care Medicine Department, Cairo University Hospitals and all its members for all the help and support.The authors thank Walid Salah at Analysis, Cairo, Egypt for his laboratory assistance.

Funding

This study was completely self funded.

Conflicts of interest

None to declare.

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Naglaa Samir Bazan
    • 1
    Email author
  • Nirmeen Ahmed Sabry
    • 2
  • Amal Rizk
    • 3
  • Sherif Mokhtar
    • 4
  • Osama Badary
    • 5
  1. 1.Critical Care Medicine DepartmentCairo University HospitalsCairoEgypt
  2. 2.Faculty of Pharmacy, Clinical Pharmacy DepartmentCairo UniversityCairoEgypt
  3. 3.Faculty of Medicine, Critical Care Medicine DepartmentCairo UniversityCairoEgypt
  4. 4.Faculty of Medicine, Critical Care Medicine DepartmentCairo UniversityCairoEgypt
  5. 5.Faculty of Pharmacy, Clinical Pharmacy DepartmentAin Shams UniversityCairoEgypt

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