In Vitro Evidences for Simvastatin and Losartan Potassium Interaction and Its in Vivo Implications

Abstract

In the present paper, we describe the in vitro availability of simvastatin, a potent HMG-CoA reductase inhibitor, in presence of losartan potassium, which is a non-peptide angiotensin II receptor antagonist. These studies were carried out at 37, 48 and 60°C in different pH environments simulating human body compartments. The reactions were studied by UV spectroscopy and the availability of both drugs in presence of each other was determined by deriving a simultaneous equation for two component system through modification of Beer`s law. The interactions were further characterized by IR and H 1 NMR spectroscopic techniques. It was observed that availability of simvastatin in presence of losartan at 37 ºC in simulated gastric juice, at pH 7.4 and pH 9.0 was blocked by losartan through the formation of a charge-transfer complex while the availability of losartan in turn was immensely increased. In pH 4.0 these effects were reversed, availability of simvastatin increased and the availability of losartan was depressed. Similar results were observed at higher temperatures.