Int. J. Pharm. Sci. Rev. Res., 53(1), November - December 2018; Article No. 15, Pages: 77-87 ISSN 0976 – 044X International Journal of Pharmaceutical Sciences Review and Research Available online at www.globalresearchonline.net © Copyright protected. Unauthorised republication, reproduction, distribution, dissemination and copying of this document in whole or in part is strictly prohibited. 77 Farah Al-Mamoori 1* , Kenza Mansoor 1 , Eyad Mallah 1 , Feras Elhajji 2 1 Department of Pharmaceutical medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman-Jordan. 2 Department of Pharmacy and Medical Sciences, Applied Science University, Amman-Jordan. *Corresponding author’s E-mail: farahalmaamori@yahoo.com Received: 28-09-2018; Revised: 30-10-2018; Accepted: 10-11-2018. ABSTRACT Complementary and alternative medicines (CAM), specifically herbal medicine, has been used since antiquity for the treatment of different ailments. However, a large number of studies on minor and significant drug–herb interactions have been recently reported since many people believe that “herbal products are harmless”. The study was conducted regarding the pharmacodynamic (PD) and pharmacokinetic (PK) interaction between a warfarin and some commonly used CAMs (turmeric, hawthorn and cinnamon). To address this aim, Prothrombin Time (PT) and International Normalized Ratio (INR) were monitored. In vivo studies were conducted on Wistar laboratory rats and were divided into multiple and single dosing groups. Besides, they were analyzed by using High performance liquid chromatography (HPLC). It was developed and validated over concentration range100-4000 ng/ml of warfarin. The mobile phase was (40% acetonitrile, 60% water with triethylamine 1 ml/1L), BDS herpasil C18colum (150mm x4.6 mm, 5μm), 1. 0 ml/min flow rate, 20μl auto-sampler injection volume and metronidazole as an internal standard. The pharmacodynamic results showed that the three CAMs contributed to a significant (p<0.05) increase in PT and INR of warfarin. The pharmacokinetic results showed that no significant difference (p>0.05) in mean plasma concentration of warfarin and pharmacokinetic parameters (C max, AUC, t0.5, Kel) when combined with CAMs. The type of interaction between warfarin in combination with turmeric, hawthorn and cinnamon is a pharmacodynamic interaction. Therefore, patients using warfarin as an anti-coagulant have to use these herbal medicines cautiously. Keywords: Warfarin, Complementary and alternative medicine (CAM), Turmeric, Hawthorn, Cinnamon, Drug-herb interaction INTRODUCTION omplementary and Alternative Medicines (CAMs) is a highly various group of approaches to health care and are based on philosophies towards health and illness that are essentially different from the approach of conventional, biomedicine and pharmacy 1 . Herbal medicine (HM) is described as “holistic” system of healing together with a distinct tactic to the diagnosis and treatment of a wide range of complaints 1 . Drug-Herb Interaction (DHI) is an important issue affecting the efficacy and clinical safety of therapeutic treatment. There have been an increasing number of reports on significant DHI worldwide. Due to the popularity of using herbal products, and using multiple medicines, this has significantly increased the risk of potential interactions, especially in the elderly or specific groups of consumers 2 . The risk of interaction is increased if HMs are used concurrently with drugs which have a narrow therapeutic index like warfarin 3 . HMs are gaining popularity these days. Turmeric, hawthorn and cinnamon. Turmeric (Curcuma longa) is extensively used as a spice, food preservative and coloring material for thousands of years, it has been reported that it exerts significant effect on arthritis, alzheimer’s disease, cancer therapy, and antimicrobial activity 4-7 . Hawthorn (Crataegus spp.) has been as a medicinal material and food for hundreds of years. It is used for cardiovascular conditions such as: heart failure, hypertension, angina and arrhythmias. Furthermore, it is used for sexual dysfunction 8-10 . Cinnamon (Cinnamomum spp.) is known and widely used in the ancient world, as a popular cooking spice and traditional medicine. It is used in Type 2 Diabetes, improves the insulin resistance in women with poly cystic ovary syndrome (PCOS), in addition to its antimicrobial activity 11-13 . Warfarin is one of the most widely used anticoagulants worldwide for prophylaxis and treatment of venous thrombosis and its extensions, reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke 14 . This study was aimed to investigate the pharmacodynamic and pharmacokinetic interaction between warfarin and some commonly used CAMs (turmeric, hawthorn and cinnamon). Also, to develop and validate chromatographic methods for the simultaneous estimation of warfarin and some commonly used CAMs in rat plasma. Pharmacodynamic and Pharmacokinetic Interaction of Warfarin in the Presence of Some Commonly Used Complementary and Alternative Medicines (CAMs) in Rat Plasma by Using HPLC C Research Article