• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.768-774
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• 1999

Background: It is well known that rifampin decreases the hypoprothrombinemic effect of warfarin by induction of cytochrome P-450 enzyme in healthy volunteer. However, in patients the dosage schedule of warfarin during rifampin therapy is not established. Therefore, patients taking both rifampin and warfarin were reviewed to find out the adequate dosage schedule of warfarin in addition to side effects by interaction of two drugs. Method: Patients taking both rifampin and warfarin were retrieved from patients who were admitted due to heart disease and tuberculosis at Boochun Sejong Hospital from January of 1995 to August of 1999. To decide the adequate dosage of warfarin, the dosage of warfarin before, during, and after rifampin was evaluated in patients who kept adequate hypoprothrombinemic effect of warfarin during rifampin. To decide the adequate dosage schedule of warfarin, the time interval from the beginning of rifampin to normalization of prothrombin time(INR$\geq$1.1) was evaluated. And, the side effects by interaction of two drugs were reviewed. Results: All 12 patients taking both rifampin and warfarin were retrieved. Among them only 6 kept adequate hypoprothrombinemic effect of warfarin during rifampin. The dosage of warfarin during rifampin was $2.4{\pm}0.6$(mean$\pm$standard deviation) times as much as that before rifampin but the dosage after rifampin was the same as that before rifampin. The time interval from the beginning of rifampin to normalization of prothrombin time was $5.8{\pm}2.9$(mean${\pm}$standard deviation) days. 2 out of 12 had complication related to the interaction of rifampin and warfarin, one cerebral embolism just after the beginning of rifampin and the other cerebral hemorrhage just after the discontinuation of rifampin. Conclusion: When both rifampin and warfarin are prescribed, it would be a possible method to be confirmed by prospective study that warfarin be gradually increased about 2 times more than that without rifampin over 1 week or so after the beginning of rifampin and be tapered to the same dosage as that before rifampin when rifampin is discontinued. And, it would be prudent that prothrombin time be monitored frequently during rifampin and warfarin therapy, especially the beginning or discontinuation of rifampin.

• YAKHAK HOEJI
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• v.58 no.1
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• pp.40-46
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• 2014

Drugs with a narrow therapeutic index (NTI) require very precise dosing. Warfarin and digoxin are the examples of NTI-drugs and dosing of them varies widely for different patients. However, in South Korea, only two strengths of warfarin and one of digoxin are commercially available. This is a big barrier for the precise dispensing and has potential safety risks to patients, particularly to elderly patients. To find a potential solution to the problem, an analysis of the prescribed doses and dispensing patterns of those drugs was performed. Data were collected by computer-facilitated prescription review in a university hospital. The period screened was from May 1st, 2012 to April 30th, 2013. All the prescriptions with either warfarin or digoxin tablets were selected for this study and dispensing patterns were analyzed according to the prescribed doses. A total of 17,017 warfarin prescriptions were analyzed; 8,148 for inpatient prescriptions, 8,869 for outpatient prescriptions, respectively. Of the 23 kinds of prescribed doses, 2 mg (19.9%) was most frequent, followed by 3 mg (13.2%) and 2.5 mg (11.7%). By analyzing the dispensing patterns, 60.3% (10,253) of the prescriptions required pill splitting and 72.0% of them were for the patients 65 years old and over. On the other hand, 4,350 digoxin prescriptions were included in this study. Of the 6 kinds of prescribed doses, 0.125 mg (71.2%) was most frequent, followed by 0.0625 mg (20.2%). Among the prescriptions for digoxin, 92.0% (3,998) should be split and 65.7% of them were for the patients aged 65 years and over. Despite limitations of strengths, various doses of warfarin and digoxin were prescribed. Furthermore, more than half of the prescriptions that required pill splitting were for elderly patients. The results from this study suggest that different strengths of warfarin and digoxin should be provided for accuracy of dispensing and safety for patients receiving them.

• The Korean Journal of Pharmacology
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• v.30 no.2
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• pp.255-260
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• 1994

There are some reports about the influences of free fatty acids on the albumin binding of drugs. But they were concerned to the limited free fatty acids, mostly of azapropazone-warfarin bidning site bound drugs and determination of dissociation and association constants by stopped flow technique. These data were not enough to make conculsions for the general tendency of free fatty acid to albumin binding. Therefore the influence of various saturated fatty acids of $C_{10{\sim}20}$, oleic acid and linoleic acid as unsaturated fatty acids to albumin binding of warfarin and dansylsarcosine were studied by equilibrium dialysis. The concentration of free drug was determined by spectrophotometer according to the molar ratios of 0, 0.5, 1, 2 and 4 between free fatty acid and albumin. There were significant increasing in the free durg concentration of warfarin and dansylsarcosine when the molar ratio for capric acid, lauric acid and palmitic acid was 4. The free warfarin concentration was increased significantly at a molar ratio of 4 between oleic acid and albumin. Therefore the albumin binding of durgs can be variated significantly by increased free fatty acid of diabetics and cause to the pharmacokinetic variation between healthy and diabetics.

• Journal of Veterinary Clinics
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• v.20 no.1
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• pp.74-78
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• 2003

We executed this experiment to observe side effects of warfarin, the anticoagulant that is used for preventing thrombus in cardiovascular surgery for calves. The 6 calves(70-130 kg) were used in this experiment regardless of sexes. We administered warfarin at 0.07 mg/kg daily for 25 days. Blood was collected before warfarin administration, every five days for 30 days. PCV, RBC, WBC, fibrinogen, total protein and platelet as blood test, prothrombin time (PT) as blood coagulation test, and AST, SDH, total bilirubin, BUN and creatinine as serum biochemical tests were measured. As the result of the experiment, PT has been gradually increased after warfarin administration. It has been gradually increased and remains within the therapeutic range from the third day to the 28th day. PCV and RBC were decreased significantly from the value before the administration (p < 0.05). In the serum biochemical test, SDH shows significant increase comparing the value before the administration (p < 0.05). AST and total bilirubin were increased gradually from the value before the administration. Considering the result of the experiment, to give wafarin to prevent thrombus in cardiovascular surgery, we can get anticoagulation effect with minimal administration(0.07 mg/kg, PO) from the third day of the administration. However because of the decreased PCV and RBC, it may cause anemia. It may cause damage to liver based on the result of serum biochemical test.

• YAKHAK HOEJI
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• v.53 no.2
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• pp.83-88
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• 2009

Warfarin is the most widely used oral anticoagulant in the world but maintenance of proper therapeutic range and prevention of adverse drug events always need to be careful. Especially, in Korea, warfarin dosing for patients with cerebral infarction is currently based on the nomogram which is done by foreign clinical trials not for the Korean. Therefore we evaluate warfarin dose of patients in the neurology and eventually get the base data of warfarin nomogram for Korean with stroke. We performed this study retrospectively on reviewing the medical charts to evaluate the prescribed loading dose (LD) and maintenance dose (MD) of warfarin and each responding International Normalized Ratio (INR) with any bleeding adverse drug reaction including of patient's characteristics for total 75 patients with stroke in the department of neurology of Kangnam ST. Mary's Hospital from January 2005 to June 2008. All evaluated patients should not be treated with warfarin in the past at all and should be initiated warfarin therapy first.ly at this time. All evaluated patients were divided as two classes by wafarin LD which is; 1) HDG - a high loading dosing group prescribed over 5mg, and 2) LDG - a low loading dosing group prescribed 5mg or below. As a result, average LD was $9.34{\pm}0.22$ mg (p=0.000) in HDG and $4.25{\pm}0.39$ mg (p=0.000) in LDG. Average baseline INR was $0.91{\pm}0.05$ (p=0.161) in HDG and $1.26{\pm}0.14$ (p=0.002) in LDG. On the first and second week, daily MD was $4.21{\pm}0.14$ mg (p=0.000) and $2.96{\pm}0.19$ mg (p=0.696) in HDG and also in LDG, $2.95{\pm}0.29$ mg (p=0.000) and $3.14{\pm}0.36$ mg (p=0.696). Also average reacting daily INR was respectively $2.53{\pm}0.12$ (p=0.141) and $2.51{\pm}0.16$ (p=0.678) in HDG, and in LDG, $2.11{\pm}0.17$ (p=0.141) and $2.42{\pm}0.14$ (p=0.678). After the second week, INR was not measured in regularly. Also most of underlying diseases were hypertension (n=38), diabetes mellitus (n=14), dyslipidemia (n=8) in order. Four ADRs with simple hemorrhage were occurred and those were due to drug interaction by comedication. In the conclusion, proper starting LD for Korean with stroke is 10 mg if baseline INR is around 1.0 or 5 mg if over 1.3. Proper MD need to be more evaluated in the future for setting up warfarin nomogram to make prospective study.

• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.464-472
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• 2007

Objectives : Nowadays the combined use of oriental herbal medicines and western biomedical medicines has been prevalent but controversial. Warfarin has been much reported to interact with some herbal medicines so that it influences prothrombin time(PT) & international normalized ratio(INR). This study was aimed to examine how much warfarin interacts with herbal medicines during treatment of stroke patients Methods : This was a retrospective case control study of 53 patients whowere treated with concomitant treatment of herbal medicines & warfarin. They were within normal limit in liver function, renal function, hematocrit, hemoglobin, and platelet count at first admission lab. We classified them into 2 classes: study group (taking herbal medicines including Panax ginseng, Angelica sinensis, Zingiber officinale, Salvia miltiorrhiza that were reported to interact with warfarin to impact PT (INR) and control group (taking other herbal medicines). We followed up PT (INR) at 5-10 days interval with AST, ALT, BUN, creatinine, hematocrit, hemoglobin, and platelet count. Results : AST, BUN, creatinine, hemoglobin, hematocrit, and platelet count were not changed significantly between first and final tests during the admission period. Only ALT decreased significantly in the control group. Neither baseline nor peak PT (INR) was significantly different between the groups. However, only warfarin dose was significantly correlated with PT and INR (r=0.810, r=0.798, p<0.01). Conclusions : It was concluded that PT(INR) was not influenced with herbal medicines and warfarin but by far dependent on warfarin dose in stroke patients restricted with normal liver function, renal function, and hematocrit, hemoglobin, and platelet count. Further prospective study is needed on larger samples to conclude that the combined therapy of herbal medicines and warfarin is safe.

• Journal of Chest Surgery
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• v.49 no.5
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• pp.329-336
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• 2016

Background: Guidelines for esophagogastroduodenoscopy (EGD) in the West allow the continued use of warfarin under therapeutic international normalized ratio (INR) level. In Korea, no guidelines have been issued regarding warfarin treatment before EGD. The authors surveyed Korean cardiac surgeons about how Korean cardiac surgeons handle warfarin therapy before EGD using a questionnaire. Participants were requested to make decisions regarding the continuation of warfarin therapy in two hypothetical cases. Methods: The questionnaire was administered to cardiac surgeons and consisted of eight questions, including two case scenarios. Results: Thirty- six cardiac surgeons at 28 hospitals participated in the survey, and 52.7% of the participants chose to stop warfarin before EGD in aortic valve replacement patients without risk factors for thromboembolism. When the patient's INR level was 2, 31% of the participants indicated that they would choose to continue warfarin therapy. For EGD with biopsy, 72.2% of the participants chose warfarin withdrawal, and 25% of the participants chose heparin replacement. In mitral valve replacement patients, 47.2% of the participants chose to discontinue warfarin, and 22.2% of the participants chose heparin replacement. For EGD with biopsy in patients with a mitral valve replacement, 58.3% of the participants chose to stop warfarin, and 41.7% of the participants chose heparin replacement. Conclusion: This study demonstrated that attitudes regarding warfarin treatment for EGD are very different among Korean surgeons. Guidelines specific to the Korean population are required.

• Analytical Science and Technology
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• v.5 no.1
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• pp.83-90
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• 1992

The $^{14}C$-warfarin used as rodenticids was identified from various organs of sprague dawley with scintillation counter. And the cytochrome p-450 which was induced by coumarin derivatives was identified with electrophoresis. The distributions of $^{14}C$-warfarin after $14.8{\mu}Ci/kg$ oral application at each organ was as follows; urine-7.5%, blood-0.44%, feces-0.9%, liver-0.66%, lung-0.86%, kidney-0.8%, heart-0.43% and spreen-0.33% after 24hrs. The cytochrome p-450 was purified by Octyl Sepharose CL-4B hydrophobic chromatography and isozymes were 50.8 Kd in control group, 53.3 Kd and 55.2 Kd in coumarin pretreated group and 50.8 Kd, 54.6 Kd and 57.7 Kd in warfarin pretreated group.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.2
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• pp.175-181
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• 2010

Objectives : The purpose of this study is to investigate interaction and safety in administering herb-medicine with warfarin. Methods : For this study, we selected 19 patients who have been taking warfarin, from the ones that have been transferred from western hospital to oriental hospital. During their stay in the oriental hospital, we gave herb-medicine in addition to warfarin. Then we gathered informations and data on sex, age, main indications, and International Normalized Ratio(INR) values of selected patients through Electronic Medical Records(EMR) of Dong-Guk university hospital. Accordingly, we compiled all of the above data for a period of 10 days prior and 10 days post admission(western hospital period and oriental hospital period, respectively). Results and Conclusions : The statistical analysis of the data have revealed that there was no significant change of INR values after giving herb-medicine with warfarin(p=0.586). The result shows that administration of herb-medicine with warfarin is safe and has little drug interaction. However, this study was carried out on small sample size and the interaction with other drugs and various kinds of herb-medicine was not considered. Although we attained a restrictive result from this study, we are able to suggest the safety about co-administration of herb-medicine and warfarin.

• YAKHAK HOEJI
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• v.49 no.2
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• pp.134-139
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• 2005

Warfarin is a widely used oral anticoagulant agent used to treat thromboembolic disease. The purpose of this study was to develop the efficient assay method of warfarin sodium i n human plasma and to assess the pharmacokinetic profile of the warfarin in healthy Korean volunteers. The pharmacokinetics of warfarin administered orally was evaluated after a dose of 10 mg. Warfarin in plasma was assayed using a specific HPLC method with UV absorbance at 304 nm. AUC was 46.33${\pm}9.95{\mu}g/ml.hr$, $C_{max}$ $1.22{\pm}0.22{\mu}g/ml, $T_{max}$$2.50{\pm}1.41$ hr and half-life $43.49{\pm}4.33$ hr. $T_{max}$ was slightly shorter than that in Caucasian (3~9 hr), whereas the half-life was longer than that in Caucasian (10~45 hr, mean: 36 hr). These results suggest that warfarin may have a longer duration in Korean than in Caucasian.