Evaluation of methods for achieving stable INR in healthy subjects during a multiple-dose warfarin study.
Purpose: No consistent method is available for finding stable warfarin maintenance doses and fast stabilization of international normalized ratio (INR) values among healthy subjects in experimental warfarin interaction studies. Using data from an earlier study that targeted a stable INR of 1.5-2.0 t...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 68; no. 3; pp. 239 - 248 |
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| Autores principales: | , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Mar2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104515446&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104515446 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Mar2012 vid: 68 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104515446 71509368 10.1007/s00228-011-1114-4 NLM21881887 104515446 ppf: 239 ppct: 9 formats: fmt: @attributes: type: P tig: atl: Evaluation of methods for achieving stable INR in healthy subjects during a multiple-dose warfarin study. aug: au: Chappell, Jill Dickinson, Gemma Mitchell, Malcolm Haber, Harry Jin, Yan Lobo, Evelyn affil: Eli Lilly and Company, Lilly Corporate Center Indianapolis 46285 USA sug: subj: Warfarin Administration and Dosage International Normalized Ratio Warfarin Pharmacodynamics Human Retrospective Design Warfarin Pharmacokinetics Secondary Analysis Male Female Adult Middle Age United Kingdom Data Analysis Software Warfarin Blood Kruskal-Wallis Test Chi Square Test Survival Analysis Analysis of Variance Cox Proportional Hazards Model Coefficient alpha Two-Tailed Test Regression Computer Simulation Polymorphism, Genetic Descriptive Statistics Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: Purpose: No consistent method is available for finding stable warfarin maintenance doses and fast stabilization of international normalized ratio (INR) values among healthy subjects in experimental warfarin interaction studies. Using data from an earlier study that targeted a stable INR of 1.5-2.0 to test an interaction, we retrospectively evaluated potential dosing algorithms using all methods available to us to decrease the time needed for INR stabilization, which could be useful for future interaction studies in healthy subjects. Methods: Published pharmacogenetic and clinical dosing algorithms used to initiate pharmacotherapy with warfarin were applied, predicted doses and actual doses were compared by regression analysis, and concentration-time profiles of S-warfarin were simulated using SimCYP® software. Results: No demographic variables were significantly associated with time to reach a stable, low-intensity INR in this population of relatively young, healthy subjects. Predicted and actual doses were positively correlated for the pharmacogenetic algorithm, but not for the clinical algorithm. INR levels and S-warfarin concentrations were associated with CYP2C9 and VKORC1 genotypes. Conclusions: Induction to a pharmacodynamic steady state for warfarin for future multiple-dose warfarin drug-interaction studies in healthy volunteers may be predicted using a pharmacogenetic-based dosing algorithm. Simulations revealed that the desired subtherapeutic INR level may be achieved by reducing the predicted dose by approximately 15%. Further study is needed to assess the applicability of this approach to decrease attrition rates and the time needed to reach INR stabilization. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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