Zafar Shamaila, Ashraf Muhammad Mudassar, Ali Asghar, Aslam Nosheen, Ashraf Asma, Zafar Sara, Andleeb Rahat, Khadam Muhammad Waqas, Tahir Imtiaz Mahmood, Akram Muhammad, Shah Syed Muhammad Ali, Daniyal Muhammad
Department of Physiology, Government College University, Faisalabad, Pakistan / Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan.
Department of Eastern Medicine, Directorate of Medical Sciences, Government College University Faisalabad, Pakistan.
Pak J Pharm Sci. 2018 Mar;31(2(Suppl.)):611-616.
Drug-drug interactions are most commonly occurring phenomenon in clinical practice. Many physicians are afraid of being involved in an allegation of malpractices due to the occurrence of any severe interaction. These interactions not only occur between drugs but also between any kind of food, tobacco smoke, caffeine and alcohol etc. Therefore, the present study was directed to inspect the effect of caffeine on the anticoagulation activity of warfarin in healthy adult male albino rabbits. Blank blood samples were collected from each rabbit. Rabbits were given warfarin (0.5mg kg-1) orally via stomach tube and blood samples were collected in PT/INR vials at various intervals. After a washout period of 14 days, warfarin was orally administrated at same dose rate along with caffeine (5 mg kg-1 every twelve hours for three days) and same sampling schedule was repeated. Prothrombin time (PT) and the international normalized ratio (INR) of blood samples were determined to estimate changes in the anticoagulation activity of warfarin after its concurrent administration with caffeine. The PT data revealed that R and AUC increased significantly (P<0.05) from 1991.6 and 60.5 to 2124.8 and 67.5, respectively, before and after co-administration. Similarly, a significant (P<0.05) increase was observed in R and AUC of INR from 6.42 and 153.7 to 7.4 and 167.5, respectively, alone and along with caffeine. However, no change was observed in T associated with PT and INR either the drug was administered alone or in combination with caffeine. It was concluded that caffeine has the capacity to inhibit the metabolism of warfarin and enhance its plasma concentration and hence anticoagulant effects. Thus, patients should be advised to limit the frequent use of caffeine-rich products i.e. tea and coffee during warfarin therapy.
药物相互作用是临床实践中最常见的现象。许多医生担心因发生任何严重相互作用而被指控存在医疗过失。这些相互作用不仅发生在药物之间,还发生在任何种类的食物、烟草烟雾、咖啡因和酒精等之间。因此,本研究旨在考察咖啡因对健康成年雄性白化兔华法林抗凝活性的影响。从每只兔子采集空白血样。通过胃管给兔子口服华法林(0.5mg/kg-1),并在不同时间间隔在PT/INR试管中采集血样。经过14天的洗脱期后,以相同剂量率口服华法林并同时给予咖啡因(每12小时5mg/kg-1,共三天),并重复相同的采样方案。测定血样的凝血酶原时间(PT)和国际标准化比值(INR),以评估华法林与咖啡因同时给药后其抗凝活性的变化。PT数据显示,联合给药前后,R和AUC分别从1991.6和60.5显著增加(P<0.05)至2124.8和67.5。同样,单独给药和与咖啡因联合给药时,INR的R和AUC分别从6.42和153.7显著增加(P<0.05)至7.4和167.5。然而,无论药物单独给药还是与咖啡因联合给药,与PT和INR相关的T均未观察到变化。得出的结论是,咖啡因有能力抑制华法林的代谢并提高其血浆浓度,从而增强抗凝作用。因此,应建议患者在华法林治疗期间限制频繁使用富含咖啡因的产品,即茶和咖啡。