scholarly journals Lack of effect of Imrecoxib, an innovative and moderate COX-2 inhibitor, on pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yani Liu ◽  
Rui Zhang ◽  
Zhongfang Li ◽  
Jiali Zhou ◽  
Tingyu Yang ◽  
...  
Keyword(s):  
Geometric Mean ◽  
International Normalized Ratio ◽  
Healthy Male ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Good Tolerance ◽  
Osteoarthritis Pain ◽  
Dose Warfarin ◽  
Cox 2 ◽  
Pain Symptoms ◽  
Warfarin Enantiomers

Abstract Imrecoxib is a registered treatment for osteoarthritis pain symptoms in China. This study aims to assess the effect of imrecoxib on the pharmacodynamics and pharmacokinetics of warfarin. 12 healthy male volunteers with CYP2C9*3 AA and VKORC1 AA genotypes took a 5 mg dose of warfarin both alone and concomitantly with steady-state imrecoxib. Both warfarin alone and concomitantly with imrecoxib have safey and good tolerance across the trial. Following warfarin and imrecoxib co-administration, neither Cmax, AUC0-t and t1/2 of warfarin enantiomers nor AUC of international normalized ratio (INR) were markedly different from those of warfarin alone. The geometric mean ratios (GMRs) (warfarin + imrecoxib: warfarin alone) of INR(AUC) was 1 (0.99, 1.01). The GMRs of warfarin AUC0-∞ (90% confidence interval, CIs) for warfarin + imrecoxib: warfarin alone were 1.12 (1.08, 1.16) for R-warfarin and 1.13 (1.07, 1.18) for S- warfarin. The 90% CIs of the GMRs of AUC0-∞, Cmax and INR (AUC) were all within a 0.8–1.25 interval. The combination of warfarin and imrecoxib did not impact the pharmacodynamics and pharmacokinetics of single-dose warfarin; therefore, when treating a patient with imrecoxib and warfarin, it is not required to adjust the dosage of warfarin.

Effect of Fixed Minidose Warfarin, Conventional Dose Warfarin and Aspirin on INR and Prothrombin Fragment 1 + 2 in Patients with Atrial Fibrillation

1997 ◽  
Vol 77 (05) ◽  
pp. 0845-0848 ◽  
Author(s):  
B G Koefoed ◽  
C Feddersen ◽  
A L Gulløv ◽  
P Petersen
Keyword(s):  
Atrial Fibrillation ◽  
International Normalized Ratio ◽  
Coagulation System ◽  
Nonvalvular Atrial Fibrillation ◽  
Treatment Groups ◽  
Prothrombin Fragment ◽  
Conventional Dose ◽  
Dose Warfarin ◽  
Significant Difference ◽  
Changes Over Time

SummaryThe efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well- documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combination with aspirin 300 mg/day, of conventional dose adjusted warfarin (INR 2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients with chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to investigate the effect on the coagulation system of the treatments, the International Normalized Ratio of the prothrombin time (INR) and prothrombin fragment 1 + 2 (F1 +2) were monitored at baseline and after three months of treatment in 100 patients consecutively included in the trial. At baseline no differences in INR and F1+2 between the four treatment groups were present. After three months of therapy the level of INR increased significantly from baseline in patients receiving warfarin in any dose and the level of F1+2 decreased significantly by combined minidose warfarin-aspirin and by dose adjusted warfarin. When comparing the changes over time in FI +2 (three-month value minus baseline value) during therapy with fixed minidose warfarin, combined minidose warfarin-aspirin and aspirin alone no significant difference between the groups was found. In conclusion, INR was changed by all three warfarin regimens but only dose adjusted warfarin (INR 2.0-3.0) had a marked effect on F1+2.

scholarly journals Continuous use of low-dose warfarin for gastric endoscopic submucosal dissection: a prospective study

2017 ◽  
Vol 05 (05) ◽  
pp. E348-E353 ◽  
Author(s):  
Hideaki Harada ◽  
Satoshi Suehiro ◽  
Daisuke Murakami ◽  
Takanori Shimizu ◽  
Ryotaro Nakahara ◽  
...  
Keyword(s):  
Endoscopic Submucosal Dissection ◽  
Low Dose ◽  
Postoperative Bleeding ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Safety And Efficacy ◽  
Submucosal Dissection ◽  
Day Range ◽  
Dose Warfarin ◽  
Significant Difference

Abstract Background and study aims Patients who receive warfarin usually require heparin bridge therapy (HBT) to prevent thromboembolic events during endoscopic submucosal dissection (ESD); however, clinical evidence demonstrating the safety and efficacy of HBT during gastric ESD is limited. Conversely, warfarin can be continuously used as a substitute for HBT to endoscopic procedures which have a low risk of bleeding. This study aimed to clarify the safety and efficacy of continuous low-dose warfarin (LDW) for gastric ESD. Patients and methods This was a prospective observational study at a single institution. A total of 22 patients who received warfarin between December 2014 and January 2016 were enrolled. The patients were treated with gastric ESD with a low dose of warfarin ( ≤ 4 mg) at approximately 1.6 – 2.6 of the international normalized ratio (INR) levels. Furthermore, we analyzed a total of 23 patients with HBT who underwent gastric ESD between January 2011 and November 2014. Results The average of warfarin dose and the INR level on the day of gastric ESD in the continuous LDW group were 2.3 mg/day (range 0.5 – 4.0) and 1.87 (range 1.41 – 2.75), respectively. Two of the 22 patients (9.1 %) in the continuous LDW group and 5 of the 23 patients (21.7 %) in the HBT group had postoperative bleeding after gastric ESD. Although the postoperative bleeding rate in the continuous LDW group was lower than that in the HBT group, no significant difference was observed between the 2 groups (P = 0.414). Conclusions Gastric ESD with continuous LDW as a substitute for HBT was feasible and may be acceptable.

Pharmacokinetics and Pharmacodynamics of Ticagrelor and Prasugrel in Healthy Male Korean Volunteers

2015 ◽  
Vol 37 (3) ◽  
pp. 563-573 ◽  
Author(s):  
Hae-Sun Jeon ◽  
Mi-Jo Kim ◽  
Hee-Youn Choi ◽  
Yo-Han Kim ◽  
Eun-Hwa Kim ◽  
...  
Keyword(s):  
Healthy Male ◽  
Pharmacokinetics And Pharmacodynamics

Effect of rifampin on the pharmacokinetics and pharmacodynamics of prasugrel in healthy male subjects

2009 ◽  
Vol 25 (8) ◽  
pp. 1821-1829 ◽  
Author(s):  
N. A. Farid ◽  
J. A. Jakubowski ◽  
C. D. Payne ◽  
Y. G. Li ◽  
Y. Jin ◽  
...  
Keyword(s):  
Healthy Male ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Male Subjects

Low-Dose Warfarin for Prevention of Symptomatic Thromboembolism after Orthopedic Surgery

2005 ◽  
Vol 39 (6) ◽  
pp. 1002-1007 ◽  
Author(s):  
Jeremy J Enyart ◽  
Ronald J Jones
Keyword(s):  
Low Dose ◽  
Weighted Average ◽  
International Normalized Ratio ◽  
Odds Ratios ◽  
Vte Prophylaxis ◽  
Dose Warfarin ◽  
Total Knee ◽  
Observational Design ◽  
Warfarin Dosing ◽  
Event Rates

BACKGROUND: Warfarin dosing with a target international normalized ratio (INR) range of 1.5–2.5 has not been reported as adequate for venous thromboembolism (VTE) prophylaxis after total knee (TKR) and total hip replacement (THR) surgery. OBJECTIVE: To evaluate the rate of symptomatic VTE after TKR and THR surgery using a low-dose (INR 1.5–2.5) warfarin protocol started the evening before surgery compared with a literature cohort treated with enoxaparin. METHODS: TKR/THR patients treated with a 21-day low-dose warfarin protocol were followed via a consecutive observational design. Main outcome measures were symptomatic VTE and pulmonary embolism (PE), with major bleeds and death as secondary outcomes. Low-dose warfarin was compared with a literature cohort of patients treated with enoxaparin who received enoxaparin for a similar length of time and was evaluated for the same outcomes. Cohort event rates were derived as a weighted average using the DerSimonian model. RESULTS: VTE, PE, bleeds, and deaths in the low-dose warfarin group were 8 (1.04%), 4 (0.52%), 8 (1.04%), and 4 (0.52%), respectively. The cohort weighted average values were 35 (1.33%), 19 (0.72%), 65 (2.46%), and 18 (0.67%), respectively. Odds ratios for low-dose warfarin for VTE, PE, and VTE plus PE were 0.778 (95% CI 0.36 to 1.68), 0.717 (0.24 to 2.11), and 0.754 (0.41 to 1.42), respectively, all nonsignificant. Odds ratios for bleeds and death were 0.420 (0.20 to 0.87; p = 0.02) and 0.756 (0.26 to 2.24; NS), respectively. CONCLUSIONS: For this evaluation, low-dose warfarin was comparable to the enoxaparin cohort for development of VTE, PE, and VTE+PE. Incidences of bleeds in the enoxaparin cohort were significantly higher than in patients receiving low-dose warfarin.

Sign in / Sign up

Export Citation Format

Share Document