Usefulness of coadministration of bucolome in warfarin therapy: pharmacokinetic and pharmacodynamic analysis using outpatient prescriptions

Ōsawa, Makiko; Hada, Nobuko; Matsumoto, Kaori; Hasegawa, Tetsuya; Kobayashi, Daisuke; Morimoto, Yasunori; Yamaguchi, Masatoshi; Kanamoto, Ikuo; Nakagawa, Teruaki; Sugibayashi, Kenji

doi:10.1016/j.ijpharm.2004.12.009

Cited by 10 publications

(12 citation statements)

References 9 publications

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“…1,5-7 In our study, bucolome reduced the dose of warfarin by 61%, similar to prior studies (58-60% decrease). 1, 6 We also found that bucolome did not affect the stability of the anticoagulant effects of warfarin. However, when bucolome is coadministered with warfarin, warfarin has to be in the powdered form, which in this study was administered in all patients in bucolome group, but did not result in increased INR fluctuation.…”

Section: Discussionmentioning

confidence: 57%

Effects of Combination Therapy With Warfarin and Bucolome for Anticoagulation in Patients With Atrial Fibrillation

Obata

Watanabe

Ito

et al. 2011

Circ J

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Background: Bucolome, a nonsteroidal antiinflammatory drug, enhances the effects of warfarin. In the present study, the effects of combination therapy (bucolome + warfarin) vs. warfarin alone on atrial fibrillation were investigated. Methods and Results:Combined therapy resulted in a decrease in the warfarin dose to approximately one-third. The fluctuations of the international normalized ratio and the time in therapeutic range were similar in both groups. There was no adverse effect in either group. Interestingly, uric acid was lower in the bucolome group. Conclusions:Bucolome enhanced the effects of warfarin, resulting in a decreased dose of warfarin without adverse effects and it showed similar anticoagulant stability to warfarin alone. (Circ J 2011; 75: 201 - 203)

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Section: Discussionmentioning

confidence: 57%

Effects of Combination Therapy With Warfarin and Bucolome for Anticoagulation in Patients With Atrial Fibrillation

Obata

Watanabe

Ito

et al. 2011

Circ J

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“…5,6) In cases of warfarin resistance, high-dose warfarin, ie, 8-12 mg or more, will be required in some cases, so bucolome combination therapy will be useful in such cases to reduce the dose of warfarin. 9) However, what is the stabilization point of warfarin action by bucolome combination? At least in some institutes, it has been thought that bucolome combination therapy stabilizes warfarin action in anticoagulation therapy, 16) but our present study could not demonstrate the superiority of bucolome combination therapy over warfarin monotherapy using the TTR index.…”

Section: Discussionmentioning

confidence: 99%

“…5,8) This is a well-known side effect of the interaction between drugs during combination therapy with NSAIDs and warfarin but, in at least some areas, combination therapy of warfarin and bucolome is employed for empirical therapy to enhance and stabilize the action of warfarin. 9) It has been reported that the efficacy of warfarin for embolism prevention depends on the time for which the action of warfarin is maintained in an appropriate therapeutic range, ie, time in therapeutic range (TTR). 10) Therefore, it would be clinically very useful if a method to stabilize the action of warfarin could be developed; however, if the combined medicine is changed in the environment of enhanced action, it could enhance the interaction, so bucolome combination therapy should be selected after careful comparative verification under certain conditions.…”

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confidence: 99%

Risks and Benefits of Combined Use of Bucolome and Warfarin in Anticoagulation Therapy

Hatakeyama

Niwano

et al. 2010

Int. Heart J.

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SummaryAlthough bucolome has been used empirically to enhance and stabilize warfarin action in some institutes, the clinical risks and benefits of this combination are unclear. In the present study, warfarin monotherapy (WM) and bucolome combination (BC) therapy were compared in anticoagulation therapy.One hundred and ninety-five patients indicated for anticoagulation therapy were randomly assigned to WM (n = 98) or BC (bucolome 300 mg/day, n = 97). The dosage of warfarin was optimized in each patient to maintain the international normalized ratio (INR) level in the appropriate zone, ie, 1.6-2.6 for lower risk and 2.0-3.0 for higher risk patients. The clinical characteristics, clinical events, and time in therapeutic range (TTR) were evaluated and compared between the two groups. TTR was calculated using Rosendaal's linear interpolation method.The optimal dosage of warfarin was 3.3 ± 1.0 mg/day in WM and 1.4 ± 0.5 mg/day in BC (P < 0.001). During the observation period of 18 ± 6 months, no serious complication was observed and INR was measured 11 ± 3 times in each case. TTR was 0.61 ± 0.13 in WM and 0.62 ± 0.14 in BC (NS), but TTR in the WM subgroup with warfarin > 3 mg (0.58 ± 0.13) was lower than in the WM subgroup with warfarin ≤ 3 mg (0.64 ± 0.13, P = 0.026) and BC (P = 0.042).BC reduced the optimal dosage of warfarin without increasing clinical events. There was no significant difference in TTR between WM and BC, but BC may have benefits in selected cases, such as warfarin resistance. (Int Heart J 2010; 51: 399-403)

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“…In the clinical setting, warfarin (WF), an anticoagulant, is used in racemic mixtures, and the anticoagulant activity of ( S )‐WF is 3‐ to 5‐fold more potent than that of ( R )‐WF . As ( S )‐WF is primarily metabolized by cytochrome P450 (CYP) 2C9, some reports have suggested that the concomitant administration of warfarin and bucolome, a CYP2C9 inhibitor, might be useful for increasing the blood level, and hence the efficacy, of ( S )‐WF . For example, Osawa et al .…”

Section: Introductionmentioning

confidence: 99%

In silico evaluation of warfarin–bucolome therapy

Ohtani

Hakoda

Imaoka

et al. 2016

Biopharm & Drug Disp

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The σ values in the presence and absence of bucolome were predicted to be 0.73 and 0.68, respectively, suggesting that bucolome might increase the inter-patient variation, as clinically observed. In the prediction study, the σ value of the bucolome co-administered group was greater in almost all of the examined conditions. In conclusion, the concomitant administration of bucolome might not be useful for reducing the inter-patient variation of (S)-warfarin pharmacokinetics. Copyright © 2016 John Wiley & Sons, Ltd.

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Usefulness of coadministration of bucolome in warfarin therapy: pharmacokinetic and pharmacodynamic analysis using outpatient prescriptions

Cited by 10 publications

References 9 publications

Effects of Combination Therapy With Warfarin and Bucolome for Anticoagulation in Patients With Atrial Fibrillation

Effects of Combination Therapy With Warfarin and Bucolome for Anticoagulation in Patients With Atrial Fibrillation

Risks and Benefits of Combined Use of Bucolome and Warfarin in Anticoagulation Therapy

In silico evaluation of warfarin–bucolome therapy

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