Drug-drug interaction is an important issue in clinical practice as well as in the discovery and development of new drugs. A large number of medications is used simultaneously that may increase the risks for drug interactions. The therapeutic effects of drugs may exhibit independently or may interfere or interact with each other. The interaction may be agonist or antagonist of one drug by another. Sometimes, multiple drug therapy is favorable to the patients and sometimes it causes serious adverse effects. Therefore, combinations of drugs chosen for investigation of drug-drug interactions are selected for alteration in the pharmacokinetics or pharmacodynamics of a narrow therapeutic index drug (Saha et al., 2013). Thus the drug interaction study is very much important in respect to both bio-pharmaceutics and pharmacology (Goodman, 1996; Saha et al., 2015).
Andrographis paniculata (Burm. f.) Wall. Ex Nees belongs to the family of Acanthaceae which is called as Kalmegh or King of Bitters (Mishra, Sangwan, & Sangwan, 2007; Rajani, Shrivastava, & Ravishankara, 2000). It is an herbaceous plant and is found in tropical and subtropical Asia, Southeast Asia, and India (Jarukamjorn & Nemoto, 2008). It has wide range of pharmacological application, which has been used either single or in combination with other drugs in various Indian traditional systems of medicine like Ayurveda and Sidda. Traditionally, mostly leaves and roots are used for different medicinal purposes in Asia and Europe that is also known as folklore remedy or as herbal supplement for health promotion or ailments (Jarukamjorn & Nemoto, 2008). It possesses several phytochemical constituents with unique and interesting biological properties.
The bioactive compound ‘andrographolide’ is one of the major components of the plant A. paniculata. Andrographolide is a highly bitter, colorless crystalline compound (Mishra et al., 2007). Andrographolideis chemically described as 3??, 14, 15, 18-tetrahydroxy-5??, 9??H, 10??-labda-8, 12-dien-16-oic acid ??-lactone (Fig 1 A). The melting point of this compound is 228 ºC- 230 ºC and the ultraviolet spectrum in ethanol, ?max is 223 nm. Traditionally it is used in the treatment of gastro-intestinal tract and upper respiratory infections, fever, herpes, sore throat, and a variety of other chronic and infectious disease (Mishra et al., 2007). In traditional Chinese medicine, it is a significant for cold property which is used to throw out the body-heat and to disperse toxins of the body (Deng, 1978; Jarukamjorn & Nemoto, 2008). The Indian Pharmacopoeia reports that it is a predominant constituent of at least 26 Ayurvedic formulations (Jarukamjorn & Nemoto, 2008; Mishra et al., 2007; WHO media center, 2007). It is commonly used for the prevention or treatment of cold in Scandinavian countries (Cáceres, Hancke, Burgos, & Wikman, 1997; Jarukamjorn & Nemoto, 2008).
Mirabegron is a potent ß3-adrenoceptor agonist that is recently approved by Food and Drug Administration for the prospective treatment of overactive bladder therapy (Takasu et al., 2007). The chemical name of mirabegron is (R)-2-(2-aminothiazol-4-yl)-4’-[2-[(2-hydroxy-2-phenylethyl) amino] ethyl] acetanilide or 2-amino-N-[4-[2-[[(2R)-2-hydroxy-2-phenylethyl] amino] ethyl] phenyl]-4-thiazoleacetamide (Fig 1 B).
Suvorexant is a selective, dual orexin receptor antagonist and the first drug in its class to reach the market. IUPAC name of suvorexant is [(7R)-4-(5-chloro-1, 3-benzoxazol-2-yl)-7-methyl-1, 4-diazepan-1-yl]-[5-methyl-2-(triazol-2 yl) phenyl] methanone (Fig 1 C). It is a medication for the treatment of insomnia which is characterized by difficulties with sleep onset and/or sleep maintenance approved in the United States and Japan in late 2014 (Baxter et al., 2011; Patel, Aspesi, & Evoy, 2015; Sutton, 2015). Some people reported that the drug caused a sleep disturbance such as a nightmare, sleep terror, or abnormal dream or to be more awake or even thoughts of suicide (Jacobson, Callander, & Hoyer, 2014; Teresa Carr, 2016).
The principal purpose of the present study was to investigate complex formation for synthesizing new molecule with biological activity which could be due to interaction of andrographolide and suvorexant; andrographolide and mirabegron, and suvorexant and mirabegron.
Fig 1: Chemical structure of A) andrographolide (Nanduri et al., 2004), B) mirabegron (Takusagawa, Miyashita, Iwatsubo, & Usui, 2012), and C) suvorexant (Coleman, Gotter, Herring, Winrow, & Renger, 2017)