• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.4
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• pp.228-234
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• 2020

Objectives: The number of patients undergoing oral anticoagulant therapy for cardiovascular and cerebrovascular disease is increasing. However, the risk of bleeding after tooth extraction in patients receiving warfarin is unclear. Here, we assess the risk of bleeding after tooth extraction in patients on warfarin. Materials and Methods: The study included 260 patients taking warfarin who underwent tooth extraction (694 teeth). The patients were divided into those whose teeth were extracted while they were taking warfarin, those who discontinued warfarin before extraction, and those who underwent extraction while receiving heparin bridging therapy. Bleeding complications in the two groups were compared. Results: Of the 260 patients, 156 underwent extraction while taking warfarin, 70 stopped taking warfarin before extractions, and 34 received heparin bridging therapy and stopped taking either medication before extractions. Bleeding complications occurred in 9 patients (3.5%) and 9 tooth sites (1.3%). Among the 9 patients with bleeding complications, 6 underwent extraction while taking warfarin, 2 stopped warfarin before extraction, and 1 underwent extraction after receiving heparin bridging therapy. No significant difference was seen between patient groups regarding bleeding after extractions (P=0.917). Conclusion: Warfarin use does not increase the risk of post-extraction bleeding and can therefore be continued during tooth extraction.

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.151-157
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• 2013

Purpose: Warfarin is the most widely used anticoagulant drug for preventing cardiovascular diseases after ischemic stroke and thromboembolism related to atrial fibrillation, artificial heart valves, deep vein thrombosis, and pulmonary embolism. Warfarin is commonly used in combination with other drugs such as diuretics in order to treat the comorbidity. Although several warfarin-diuretics interactions have been reported, the results are conflicting. Therefore, the initial aim of this study was to identify the effects of diuretics on the warfarin response in patients with atrial fibrillation. Methods: One hundred forty six patients with atrial fibrillation who were on anticoagulation therapy with warfarin and maintained INR levels of 2-3 for three consecutive times were followed up, retrospectively. Stable warfarin doses and INR per stable warfarin dose were compared according to age, gender, comorbidity, and concurrent medication. The stable warfarin dose was defined as the maintenance dose of warfarin of the measured patient whose INR was within the target INR range more than 3 times consecutively. Results: The differences of stable warfarin doses in patients with ($3.22{\pm}1.21$ mg/day) and without ($3.58{\pm}1.14$ mg/day) diuretics were marginally significant (P=0.069). On the other hand, stable warfarin doses were $2.97{\pm}1.10$ mg/day in patients with thiazide (n=36) and $3.58{\pm}1.14$ mg/day in patients without diuretics (n=82), which was statistically significant (p=0.009). INR values per stable warfarin dose in patients with diuretics and thiazide were $0.84{\pm}0.31$ and $0.90{\pm}0.34$, respectively, which were statistically different from those without diuretics ($0.72{\pm}0.21$, P=0.010 and P=0.006, respectively). Age, gender, and concurrent use of thiazide diuretics were found to have significant influence on the warfarin response from multivariate analysis. Conclusion: Our study showed that the concurrent use of thiazide diuretics could increase the response of warfarin in patient with atrial fibrillation. Therefore, clinicians should be aware that warfarin dose needs to be adjusted when it is used with thiazide diuretics concomitantly.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.273-278
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• 2011

The aim of this study was to investigate the effect of efonidipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of efonidipine (1 or 3 mg/kg) in rats. The effect of efonidipine on the cytochrome P450 (CYP) 3A4 activity was also evaluated. Efonidipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of $0.08{\mu}M$. Compared to those in the oral control group (warfarin without efonidipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (1 mg/kg, P<0.05; 3 mg/kg, P<0.01) by 25.9-59.0%, and the peak plasma concentration ($C_{max}$) was significantly higher (3 mg/kg, P<0.05) by 26.2% after oral administration of warfarin with efonidipine, respectively. The total body clearance of warfarin was significantly (3 mg/kg, P<0.05) decreased by efonidifine. Consequently, the relative bioavailability of warfarin was increased by 1.26- to 1.59-fold and the absolute bioavailability of warfarin with efonidipine was significantly greater by 59.7-75.4 % compared to that in the control group (47.4%). In contrast, efonidipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver and to reduction of total body celarance rather than renal elimination, resulting in reducing first-pass metabolism by efonidipine.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.493-497
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• 2011

The aim of this study was to investigate the effect of amlodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of amlodipine (0.1 or 0.4 mg/kg) in rats. The effect of amlodipine on the P-glycoprotein (P-gp) as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Amlodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of 9.1 ${\mu}M$. Compared to those animals in the oral control group (warfarin without amlodipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (0.1 mg/kg, p<0.05; 0.4 mg/kg, p<0.01) by 26.5-53.5%, and the peak plasma concentration ($C_{max}$) was significantly higher (0.4 mg/kg, p<0.05) by 26.2% after oral administration of warfarin with amlodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.26- to 1.53-fold and the absolute bioavailability of warfarin with amlodipine was significantly greater by 61.7-72.5% compared to that in the control group (47.4%). In contrast, amlodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver rather than renal elimination and P-gp by amlodipine.

• YAKHAK HOEJI
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• v.24 no.2
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• pp.97-100
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• 1980

To determine in vitro effects of phenylbutazone and niflumic acid on warfarin binding to rabbit serum protein, warfarin was added to the rabbit plasma, and the bound fraction was determined by warfarin-protein complex fluorescence. The bound fraction was decreased by phenylbtazone and niflumic acid. From this effect niflumic acid was found to have the more potent ability to displace warfarin from protein binding sites than phenylbutazone.

• Korean Journal of Clinical Pharmacy
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• v.23 no.3
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• pp.206-212
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• 2013

Purpose: The aim of this study was to investigate the effect of nimodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Methods: Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of nimodipine (0.5 or 2 mg/kg) in rats. The effect of nimodipine on the P-glycoprotein as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Results: Nimodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of $10.2{\mu}M$. Compared to those animals in the oral control group (warfarin without nimodipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (0.5 mg/kg, P<0.05; 2 mg/kg, P<0.01) by 31.3-57.6%, and the peak plasma concentration ($C_{max}$) was significantly higher (2 mg/kg, P<0.05) by 29.4% after oral administration of warfarin with nimodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.31- to 1.58-fold and the absolute bioavailability of warfarin with nimodipine was significantly greater by 64.1-76.9% compared to that in the control group (48.7%). In contrast, nimodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Conclusion: Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism rather than P-glycoprotein-mediated efflux by nimodipine.

• The Journal of Internal Korean Medicine
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• v.33 no.2
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• pp.160-171
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• 2012

Background and Objective : Warfarin is the standard anticoagulation treatment for atrial fibrillation, venous thromboembolism (VTE), and mechanical heart valves. Close monitoring of the International Normalized Ratio (INR) is required due to the drug's very narrow therapeutic window. Many factors can affect INR levels. Drug and food interactions are frequently cited as causes of adverse events with warfarin. We discussed interactions between herbs and warfarin studied in this research. Methods : In this review, PubMed was used to search medical journals. Keywords "warfarin AND interaction" were applied. Results : 55 articles were included. The possibility of correlation between warfarin and single herbal medicines such as Salviae Miltiorrhizae Radix, Angelicae Gigantis Radix, Ginseng Radix Alba, Lycii Fructus, Ginkgo Folium, Menthae Herba, Trigonellae semen was suggested. Furthermore, some herbal compounds interacting with warfarin were reported. The conclusion of studies reporting the effect of herbal medicine on warfarin were controversial due to small size or quality of research. Conculsions : We suggest that we should prescribe therapeutic herbal medicines to patients using warfarin more carefully and do INR follow-up regularly.

• Korean Journal of Bronchoesophagology
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• v.4 no.2
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• pp.235-239
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• 1998

Warfarin sodium is a widely used oral anticoagulant and it sometimes causes hemorrhage in various sites such as traumatic or operative wounds, urologic organs, gastrointesitnal tract and subcutaneous tissues. Warfarin induced hemorrhage in upper respiratory tract causing upper airway obstruction is extremely rare. Despite the life-threatening nature of this complication, the symptoms are obscure like sore throat or hoarseness, suggesting infection and early diagnosis can be delayed. Careful medical history is emphasized When bleeding is observed, the patient should be admitted for close observation and prompt treatment. Recently we have exrperienced a case of laryngeal and upper tracheal submucosal hemorrhage induced by long term warfarin in 64 years old mm. We described the case with a review of the literature.

• The Journal of the Korean dental association
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• v.57 no.10
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• pp.623-628
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• 2019

Warfarin is an anticoagulant involved in the production of vitamin K dependent blood clotting factors. Dentists should be familiar with the appropriate assessment methods and considerations for the treatment of patients taking warfarin. Dental surgery with the moderate risk of bleeding can be performed without stopping the drug through preoperative examination of the INR(international normalized ratio) value and evaluation. When performing a surgery with a high risk of bleeding, it is necessary to evaluate whether the drug can be discontinued, what the duration is, and the risk of discontinuation. Hemostasis can be obtained by local methods in most cases of postoperative bleeding in patients taking appropriately adjusted doses of warfarin.

• Journal of Trauma and Injury
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• v.34 no.1
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• pp.57-60
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• 2021

Warfarin is used as part of the treatment of various diseases, and laboratory monitoring of its effects is required. Airway hematoma secondary to warfarin is rare, but can be fatal because of potential airway obstruction. Rapid definitive airway establishment is crucial if airway obstruction is suspected. This complication is more likely to occur in those with elevated coagulation laboratory values. However, we experienced a patient in whom a massive retropharyngeal hematoma caused airway obstruction after a non-severe motor vehicle collision. The patient had been taking warfarin, and had coagulation parameter values within the normal ranges. A major fracture or hemorrhage was not anticipated. Upon examination, a massive retropharyngeal hematoma was noted. Orotracheal intubation failed due to an airway obstruction. Emergency tracheostomy and an operation for hematoma removal were performed. Physicians must always consider the possibility of airway hematoma in warfarin-taking patients with normal coagulation values regardless of the severity of mechanism of injury.