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  1. Doi SA
    Clin. Pharmacol. Ther., 1994 May;55(5):597-601.
    PMID: 8181204
    Pharmacokinetic-pharmacodynamic information regarding warfarin is used to produce a predictive model based on the idea that pharmacodynamic variability is more important than pharmacokinetic variability in the overall dose-response variability to warfarin. A modification of the maximum effect model is tested on a group of patients initiating oral anticoagulation with warfarin. Results indicate that the model can account for at least half of the total variation in maintenance doses observed (sample coefficient of determination, 0.53) and offer the physician a framework for dose requirements at the onset of therapy. The basic prediction equation is as follows: Maintenance dose = (11/international normalized ratio)-1, with a coefficient of correlation of 0.73 (95% confidence limits, 0.46-0.88). Application of this model may improve on the traditional empiric approach to warfarin dose adjustment.
    Matched MeSH terms: Warfarin/pharmacology*
  2. Iqbal MS, Muthanna FMS, Kassab YW, Hassali MA, Al-Saikhan FI, Iqbal MZ, et al.
    PLoS One, 2020;15(6):e0234734.
    PMID: 32555595 DOI: 10.1371/journal.pone.0234734
    INTRODUCTION: The effect of anticoagulation control on overall Health-Related Quality of Life (HRQoL) in patients taking warfarin in Pakistan has not been explored yet. Therefore, this study aimed to evaluate HRQoL among warfarin patients in Pakistan.

    METHODS: This cross-sectional study was conducted among patients on warfarin in Pakistan. By purposive sampling, data were collected using demographic data collection form and the World Health Organization Quality of Life: Brief Version (WHOQOL-BREF). The WHOQOL-BREF is comprised of four domains; physical, psychological, social relationships, and environment. Descriptive and inferential statistical analysis was done using SPSS version 22.

    RESULTS: Out of 295 warfarin patients, more females than males (<0.001) were observed (n = 184, 62.4%, and n = 111, 37.6% respectively). One hundred and eighteen (40.0%) patients were less than 30-years of age, whereas one hundred and seventy-seven (60.0%) patients were above 30-years of age. Mean scores for the physical (62.44±15.36), psychological (67.84±15.54), social (64.27±26.28) and environment domains (63.45±17.66) were observed.

    CONCLUSION: Patients had overall lower to moderate but satisfactory HRQoL scores in all four domains. Age, gender, employment status, education level, the indication of use and duration of warfarin therapy was associated with one or more domains of HRQoL among warfarin patients. The findings of this study would serve as a primary database for future studies. This study highlights how non-clinical factors could impact HRQoL in studied patients.

    Matched MeSH terms: Warfarin/pharmacology*
  3. Syn NL, Wong AL, Lee SC, Teoh HL, Yip JWL, Seet RC, et al.
    BMC Med, 2018 07 10;16(1):104.
    PMID: 29986700 DOI: 10.1186/s12916-018-1093-8
    BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved.

    METHODS: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy.

    RESULTS: Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference -1.16, 90% CI -1.48 to -0.84, P warfarin therapy, a pharmacogenetic algorithm meets criteria for both non-inferiority and superiority in reducing dose titrations compared with a traditional dosing approach, and performs well in prediction of actual maintenance doses. These findings imply that clinicians may consider applying a pharmacogenetic algorithm to personalize initial warfarin dosages in Asian patients.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT00700895 . Registered on June 19, 2008.

    Matched MeSH terms: Warfarin/pharmacology
  4. Bawadikji AA, Teh CH, Kader MABSA, Sulaiman SAS, Ibrahim B
    Curr Pharm Biotechnol, 2017;18(9):740-747.
    PMID: 29110602 DOI: 10.2174/1389201018666171103141828
    BACKGROUND: Warfarin, an anticoagulant medication, is prescribed regularly despite of its bleeding tendency for the prevention and/or treatment of various thromboembolic conditions, such as deep vein thrombosis, and complications associated with atrial fibrillation, and myocardial infarction, but because of its narrow therapeutic window, it has a lot of interactions with drugs and diet.

    METHODS: Warfarin relies on regular monitoring of International Normalized Ratio which is a standardized test to measure prothrombin time and appropriate dose adjustment. Pharmacometabonomics is a novel scientific field which deals with identification and quantification of the metabolites present in the metabolome using spectroscopic techniques such as Nuclear Magnetic Resonance (NMR). Pharmacometabonomics helps to indicate perturbation in the levels of metabolites in the cells and tissues due to drug or ingestion of any substance. NMR is one of the most widely-used spectroscopic techniques in metabolomics because of its reproducibility and speed.

    RESULTS: There are many factors that influence the metabolism of warfarin, making changes in drug dosage common, and clinical factors like drug-drug interactions, dietary interactions and age explain for the most part the variability in warfarin dosing. Some studies have showed that pharmacogenetic testing for warfarin dosing does not improve health outcomes, and around 26% of the variation in warfarin dose requirements remains unexplained yet.

    CONCLUSION: Many recent pharmacometabonomics studies have been conducted to identify novel biomarkers of drug therapies such as paracetamol, aspirin and simvastatin. Thus, a technique such as NMR based pharmacometabonomics to find novel biomarkers in plasma and urine might be useful to predict warfarin outcome.

    Matched MeSH terms: Warfarin/pharmacology*
  5. Teh LK, Langmia IM, Fazleen Haslinda MH, Ngow HA, Roziah MJ, Harun R, et al.
    J Clin Pharm Ther, 2012 Apr;37(2):232-6.
    PMID: 21507031 DOI: 10.1111/j.1365-2710.2011.01262.x
    Testing for cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles is recommended by the FDA for dosing of warfarin. However, dose prediction models derived from data obtained in one population may not be applicable to another. We therefore studied the impact of genetic polymorphisms of CYP2C9 and VKORC1 on warfarin dose requirement in Malaysia.
    Matched MeSH terms: Warfarin/pharmacology
  6. Bawadikji AA, Teh CH, Sheikh Abdul Kader MAB, Abdul Wahab MJB, Syed Sulaiman SA, Ibrahim B
    Am J Cardiovasc Drugs, 2020 Apr;20(2):169-177.
    PMID: 31435902 DOI: 10.1007/s40256-019-00364-2
    BACKGROUND: Warfarin is prescribed as an oral anticoagulant to treat/prevent thromboembolism in conditions such as atrial fibrillation. As there is a narrow therapeutic window, treatment with warfarin is challenging. Pharmacometabonomics using nuclear magnetic resonance (NMR) spectroscopy may provide novel techniques for the identification of novel biomarkers of warfarin.

    PURPOSE: The aim was to determine the metabolic fingerprint that predicts warfarin response based on the international normalized ratio (INR) in patients who are already receiving warfarin (phase I: identification) and to ascertain the metabolic fingerprint that discriminates stable from unstable INR in patients starting treatment with warfarin (phase II: validation).

    EXPERIMENTAL APPROACH: A total of 94 blood samples were collected for phase I: 44 patients with stable INR and 50 with unstable INR. Meanwhile, 23 samples were collected for phase II: nine patients with stable INR and 14 with unstable INR. Data analysis was performed using multivariate analysis including principal component analysis and partial least square-discriminate analysis (PLS-DA), followed by univariate and multivariate logistic regression (MVLR) to develop a model to identify unstable INR biomarkers.

    KEY RESULTS: For phase I, the PLS-DA model showed the following results: sensitivity 93.18%, specificity 91.49% and accuracy 92.31%. In the MVLR analysis of phase I, ten regions were associated with unstable INR. For phase II, the PLS-DA model showed the following results: sensitivity 66.67%, specificity 61.54% and accuracy 63.64%.

    CONCLUSIONS AND IMPLICATIONS: We have shown that the pharmacometabonomics technique was able to differentiate between unstable and stable INR with good accuracy. NMR-based pharmacometabonomics has the potential to identify novel biomarkers in plasma, which can be useful in individualizing treatment and controlling warfarin side effects, thus, minimizing undesirable effects in the future.

    Matched MeSH terms: Warfarin/pharmacology*
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