Sys Rev Pharm 2020;11(7):167-171 A multifaceted review journal in the field of pharmacy 167 Systematic Reviews in Pharmacy Vol 11, Issue 7, July-Aug 2020 Pharmacological Aspects of Statins Are Relevant to Their Structural and Physicochemical Properties Zeina Althanoon 1 , Ibrahim M Faisal 2 , Abdulla A Ahmad 1 , Marwan M. Merkhan 1 1 College of Pharmacy, University of Mosul, Mosul, Iraq. 2 College of Medicine, University of Mosul, Mosul, Iraq. Correspondence: Marwan M Merkhan, PhD Pharmacology Department of Pharmacology and Toxicology. College of pharmacy, University of Mosul, Mosul, Iraq. e-mail: marwanmerkhan@uomosul.edu.iq ABSTRACT Statins are group of hypolipidemic agents that are effective at lowering blood lipid levels subsequently improving ischemia associated pathology of atherosclerosis. This beneficial effect jointly linked to the members of statin and the miscellaneous effects they produce which is distinctly present with some statins but not others. These lipid lowering agents differ structurally and physically resulting in two group based on their hydrophobicity. Since, lipophilic penetrate readily across cell membrane, hydrophilic potentially needs a carrier and their volume of distribution is lower comparative to lipophilic statins. These structural and physicochemical variation ultimately result in variation in pharmacokinetic properties and could potentially carry an impact on their pharmacodynamics and the outcome of the therapeutic course. Moreover, variation in these properties could lead to repurposing of statin for new indications in the future. Keywords: Statin, Hydrophilic, Lipophilic, Pharmacokinetic, Pharmacodynamic. Correspondence: Marwan M. Merkhan PhD Pharmacology Department of Pharmacology and Toxicology. College of pharmacy, University of Mosul, Mosul, Iraq. e-mail: marwanmerkhan@uomosul.edu.iq mobile: 009647508662343 INTRODUCTION Lipid lowering drugs have shown to reduce the ischemic heart disease (IHD) both in patients with hyperlipidaemia and those with normal LDL-C levels. Therefore, it has been recommended to introduce some dietary changes to reduce the cholesterol level (particularly LDL-C) 1 . Various classes of medication have been introduced as hypolipidaemic agents including; bile acid-binding resins, nicotinic acid, fibrates, cholesterol-absorption inhibitors and more recently the statins, the latter are the most commonly prescribed lipid-reducing therapies 2 . The mechanism of action of statins is based on blocking the committed step in the synthesis of cholesterol; recently called the mevalonate pathway. Additionally, statins upregulate HDL-C and decrease triglyceride levels 3 . Moreover, statin exert its lipid-modifying effects through inhibition of apolipoprotein-B100 biosynthesis and reduction in biosynthesis of triglyceride-rich lipoproteins in liver 4 . Apart from their lipid-modifying effects, statins characterized by its pleiotropic effects through exerting a beneficial cardiovascular effects 5 . These newly discovered actions has been attributed to their inhibitory role in biosynthesis of non-steroidal isoprenoid compounds, an intermediary product of mevalonate pathway 6 . Statin pleiotropic effects include inhibition of inflammatory response, stimulation of repair endothelial cell injury and inhibition of smooth muscle cell proliferation 1,5 . Large clinical studies reported that statins reduced the morbidity and mortality rate in patients with or without IHD 7 . Moreover, statins have been shown to reduced progression and even encourage regression of coronary atherosclerosis, resulting in reduction in percentage of new ischemic injury and subsequently coronary occlusion in comparison to statin-untreated patients 8 . This effect has been attributed to the reduction in the core of atherosclerotic plaque resulting in prevention of plaque rupture that would initiate intramural hemorrhage/thrombosis 1 . This review article aimed at explaining the link between the differences between satins pharmacokinetics and pharmacodynamics and its correlation to structural and physicochemical properties. Diversity of statin structures Source of statins fungal derived statins include; lovastatin, pravastatin, and simvastatin, while synthetic statin include; atorvastatin, cerivastatin, fluvastatin, pravastatin, pitavastatin, and rosuvastatin 9 . Structure of statins the chemical structure of each is outlined below (see Figure 2). The principle parts of structure are three basic units; the analogue of HMG-CoA which is the target enzyme substrate and a side chain ring structure that determines their physical properties especially their solubility and pharmacokinetic; and the third part is the complex ring structure which is involved in binding of statin molecule to the HMG-CoA reductase enzyme 10 (see Figure 1).