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Article

Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation

  • Authors:
    • Jiangang Jiang
    • Ningning Ji
    • Jingliang Lan
    • Xiaoping Ge
    • Xiaoma Du
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Jinhua Hospital of TCM Affiliated to Zhejiang University of Traditional Chinese Medicine, Jinhua, Zhejiang 321000, P.R. China, Department of Cardiology, Yiwu Central Hospital, Yiwu, Zhejiang 322000, P.R. China, Department of Geriatrics, Zhejiang Jinhua Guangfu Hospital, Jinhua, Zhejiang 321000, P.R. China
  • Pages: 6144-6149
    |
    Published online on: February 6, 2018
       https://doi.org/10.3892/mmr.2018.8562
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Abstract

Warfarin is the most commonly used oral anti-coagulant in clinic practice. However, it is difficult to recommend the correct dosage due to its narrow therapeutic window. The aim of the present study was to verify the clinical value of the Lou type equation, using pharmacogenetics‑based warfarin dosing algorithms to appropriately predict the actual maintenance dose. A total of 87 Chinese Han patients who required treatment with warfarin were enrolled and randomly divided into the experimental and control groups. In the experimental group, the first 3 doses of warfarin were calculated according to the Lou type equation. While in the control group, these 3 treatments were performed following the doctors' recommendations. Then the dose of warfarin was gradually adjusted to the stable dose according to the changes in the international standardized ratio. At the end of the 50 day experimental period, there were a greater number of patients in the experimental group who exhibited a stable blood concentration of warfarin than those in the control group (83.35 and 64.4%, respectively). In addition, the mean and median times for patients to obtain a stable dose in the experimental group were significantly shorter than those in the control group (mean, 18.2±1.7 and 27.3±2.0 days; and median, 11.7±1.1 and 20.5±1.8 days, respectively). The adverse reaction rate of the experimental group (9.5%) was markedly lower than that of the control group (26.7%). The occurrence of adverse reactions in the experimental group was also significantly later when compared with the control group (43.9±1.6 and 38.6±1.5 days, respectively). Furthermore, there was no significant difference between the average predicted dose (3.4±1.1 mg/day) and the average actual dose (3.5±1.4 mg/day; P=0.313). In conclusion, using the Lou type warfarin pharmacokinetic dosing algorithm equation to administer warfarin markedly shortened the adjustment time of warfarin to reach a stable dose and reduced the adverse reactions rate, thus supporting clinical feasibility.
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1 

Yu Z, Ding YL, Lu F, Miao LY, Shen ZY and Ye WX: Warfarin dosage adjustment strategy in Chinese population. Int J Clin Exp Med. 8:9904–9910. 2015.PubMed/NCBI

2 

Baglin TP, Keeling DM and Watson HG; British Committee for Standards in Haematology, : Guidelines on oral anticoagulation (warfarin): Third edition-2005 update. Br J Haematol. 132:277–285. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Park SM, Lee JK, Chun SI, Lee HI, Kwon SU, Kang DW and Kim JS: VKORC1 and CYP2C9 genotype variations in relation to warfarin dosing in Korean stroke patients. J Stroke. 15:115–121. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Krishna Kumar D, Shewade DG, Loriot MA, Beaune P, Balachander J, Sai Chandran BV and Adithan C: Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on Warfarin maintenance dose and explicating a new pharmacogenetic algorithm in South Indian population. Eur J Clin Pharmacol. 70:47–56. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Lou Y, Hua L, Han L, Li Y, Zhang X, Tang M, Yu H, Liu Z, Wang W, Xu J, et al: Establishment and preliminary validation of Warfarin maintenance dose algorithm in Chinese Han Population. Zhonghua Xin Xue Guan Bing Za Zhi. 42:384–388. 2014.(In Chinese). PubMed/NCBI

6 

Routledge PA, Davies DM, Bell SM, Cavanagh JS and Rawlins MD: Predicting patients' warfarin requirements. Lancet. 2:854–855. 1977. View Article : Google Scholar : PubMed/NCBI

7 

Li X, Liu R, Luo ZY, Yan H, Huang WH, Yin JY, Mao XY, Chen XP, Liu ZQ, Zhou HH and Zhang W: Comparison of the predictive abilities of pharmacogenetics-based warfarin dosing algorithms using seven mathematical models in Chinese patients. Pharmacogenomics. 16:583–590. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Aithal GP, Day CP, Kesteven PJ and Daly AK: Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet. 353:717–719. 1999. View Article : Google Scholar : PubMed/NCBI

9 

Bodin L, Verstuyft C, Tregouet DA, Robert A, Dubert L, Funck-Brentano C, Jaillon P, Beaune P, Laurent-Puig P, Becquemont L and Loriot MA: Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood. 106:135–140. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Sconce EA, Khan TI, Wynne HA, Avery P, Monkhouse L, King BP, Wood P, Kesteven P, Daly AK and Kamali F: The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics up-on warfarin dose requirements: Proposal for a new dosing regiment. Blood. 106:2329–2333. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hörtnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, et al: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 427:537–541. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Zhou SF, Zhou ZW and Huang M: Polymorphisms of human cytochrome P450 2C9 and the functional relevance. Toxicology. 278:165–188. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Namazi S, Azarpira N, Hendijani F, Khorshid MB, Vessal G and Mehdipour AR: The impact of genetic polymorphisms and patient characteristics on warfarin dose requirements: A cross-sectional study in Iran. Clin Ther. 32:1050–1060. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM and Rettie AE: Association between CYP2C9 genetic variants and anticoagulation related outcomes during warfarin therapy. JAMA. 287:1690–1698. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Lane S, Al-Zubiedi S, Hatch E, Matthews I, Jorgensen AL, Deloukas P, Daly AK, Park BK, Aarons L, Ogungbenro K, et al: The population pharmacokinetics of R- and S-warfarin: Effect of genetic and clinical factors. Br J Clin Pharmacol. 73:66–76. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Rieder MJ, Reiner AP and Rettie AE: Gamma-glutamyl carboxylase (GGCX) tagSNPs have limited utility for predicting warfarin maintenance dose. J Thromb Haemost. 5:2227–2234. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Chung JE, Lee KE, Chang BC and Gwak HS: Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses. Gene. 641:68–73. 2018. View Article : Google Scholar : PubMed/NCBI

18 

Hamberg AK, Hellman J, Dahlberg J, Jonsson EN and Wadelius M: A Bayesian decision support tool for efficient dose individualization of warfarin in adults and children. BMC Med Inform Decis Mak. 15:72015. View Article : Google Scholar : PubMed/NCBI

19 

International Warfarin Pharmacogenetics Consortium, ; Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, et al: Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 360:753–764. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Cui GL, Ding H, Xu YJ, et al: High resolution melting curves (HRM) in the prevention of Warfarin initiation guide measurement genotyping and clinical application of various genotyping methods. Chin J Cardiol. 40:477–481. 2012.

21 

Deng S, Zhu G, Liu F, Zhang H, Qin X, Li L and Zhiyi H: CYP4F2 gene V433M polymorphism is associated with ischemic stroke in the male Northern Chinese Han population. Prog Neuropsychopharmacol Biol Psychiatry. 34:664–668. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Fung E, Patsopoulos NA, Belknap SM, O'Rourke DJ, Robb JF, Anderson JL, Shworak NW and Moore JH: Effect of genetic variants, especially CYP2C9 and VKORC1, on the pharmacology of Warfarin. Semin Thromb Hemost. 38:893–904. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, Deykin D and Brandt JT: Oral anticoagulants: Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest. 114 5 Suppl:445S–469S. 1998. View Article : Google Scholar : PubMed/NCBI

24 

Shahin MH, Cavallari LH, Perera MA, Khalifa SI, Misher A, Langaee T, Patel S, Perry K, Meltzer DO, McLeod HL and Johnson JA: VKORC1 Asp36Tyr geographic distribution and its impact on warfarin dose requirements in Egyptians. Thromb Haemost. 109:1045–1050. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Mushiroda T, Ohnishi Y, Saito S, Takahashi A, Kikuchi Y, Saito S, Shimomura H, Wanibuchi Y, Suzuki T, Kamatani N and Nakamura Y: Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients. J Hum Genet. 51:249–253. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Chen J, Shao L, Gong L, Luo F, Wang J, Shi Y, Tan Y, Chen Q, Zhang Y, Hui R and Wang Y: A pharmacogenetics-based Warfarin maintenance dosing algorithm from Northern Chinese patients. PLoS One. 9:e1052502014. View Article : Google Scholar : PubMed/NCBI

27 

Zhuang WF, Chen YH, Luo RP, et al: Evaluation on the stable dose prediction accuracy of Warfarin anticoagulant therapy by pharmacogenetics among Shanghai patients. Lab Med. 30:697–702. 2015.

28 

Yu LP, Song HT, Zeng ZY, Wang QM and Qiu HF: Validation and comparison of pharmacogenetics-based warfarin dosing algorithms in Han Chinese Patients. Zhonghua Xin Xue Guan Bing Za Zhi. 40:614–619. 2012.(In Chinese). PubMed/NCBI

29 

Roper N, Storer B, Bona R and Fang M: Validation and comparison of pharmacogenetics-based warfarin dosing algorithms for application of pharmacogenetic testing. J Mol Diagn. 12:283–291. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Zhao S, Zhao H, Wang X, Gao C, Qin Y, Cai H, Chen B and Cao J: Factors influencing medication knowledge and beliefs on warfarin adherence among patients with atrial fibrillation in China. Patient Prefer Adherence. 11:213–220. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Han ZH, Ren XJ and Wang Y: Anticoagulation management of patients with long-term warfarin therapy after valve replacement during the perioperative period of pacemaker implantation. Int J Clin Exp Med. 6:594–598. 2013.PubMed/NCBI

32 

Hudson M, Richard H and Pilote L: Differences in outcomes of patients with congestive heart failure prescribed celecoxib, rofecoxib, or non-steroidal anti-inflammatory drugs: Population based study. BMJ. 330:13702005. View Article : Google Scholar : PubMed/NCBI

33 

Cleland JG, Findlay I, Jafri S, Sutton G, Falk R, Bulpitt C, Prentice C, Ford I, Trainer A and Poole-Wilson PA: The Warfarin/Aspirin Study in Heart failure (WASH): A randomized trial comparing antithrombotic strategies for patients with heart failure. Am Heart J. 148:157–164. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Lu Y, Won KA, Nelson BJ, Qi D, Rausch DJ and Asinger RW: Characteristics of the amiodarone-warfarin interaction during long-term follow-up. Am J Health Syst Pharm. 65:947–952. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Zhong SL, Liu Y, Yu XY, Xu D, Tan HH, Lin QX, Yang M, Lao HY and Lin SG: The influence of genetic polymorphisms and interacting drugs on initial response to warfarin in Chinese patients with heart valve replacement. Eur J Clin Pharmacol. 67:581–590. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Jiang J, Ji N, Lan J, Ge X and Du X: Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation. Mol Med Rep 17: 6144-6149, 2018.
APA
Jiang, J., Ji, N., Lan, J., Ge, X., & Du, X. (2018). Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation. Molecular Medicine Reports, 17, 6144-6149. https://doi.org/10.3892/mmr.2018.8562
MLA
Jiang, J., Ji, N., Lan, J., Ge, X., Du, X."Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation". Molecular Medicine Reports 17.4 (2018): 6144-6149.
Chicago
Jiang, J., Ji, N., Lan, J., Ge, X., Du, X."Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation". Molecular Medicine Reports 17, no. 4 (2018): 6144-6149. https://doi.org/10.3892/mmr.2018.8562
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang J, Ji N, Lan J, Ge X and Du X: Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation. Mol Med Rep 17: 6144-6149, 2018.
APA
Jiang, J., Ji, N., Lan, J., Ge, X., & Du, X. (2018). Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation. Molecular Medicine Reports, 17, 6144-6149. https://doi.org/10.3892/mmr.2018.8562
MLA
Jiang, J., Ji, N., Lan, J., Ge, X., Du, X."Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation". Molecular Medicine Reports 17.4 (2018): 6144-6149.
Chicago
Jiang, J., Ji, N., Lan, J., Ge, X., Du, X."Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation". Molecular Medicine Reports 17, no. 4 (2018): 6144-6149. https://doi.org/10.3892/mmr.2018.8562
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