In vitro availability of atorvastatin in presence of losartan.
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are a group of cholesterol lowering agents that have become the largest selling drugs in the world. They are of proven clinical benefit in coronary heart disease, at least in those patients who do not have overt chronic heart failure (CHF). Co-administration of statins with angiotensin II receptor blockers (ARBs) is most common, since there is strong synergy between hypertension and hypercholesterolemia in terms of risk factors for the development of cardiovascular diseases. In present paper, we describe the in vitro availability of atorvastatin, 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 degrees C in different pH environments simulating human body compartments. It was observed that in pH 1, 7.4 and 9 the availability of atorvastatin was very high while losartan was not at all available. However in pH 4 these effects were reversed and atorvastatin was not available at all. At 48 degrees C the availability of atorvastatin was high and that of losartan was depressed at pH 9, whereas the later was not available at pH 1, 4 and 7.4 at all. Likewise at 60 degrees C, the availability of atorvastatin at pH 7.4 and 9 was high, whereas the charge-transfer complex formed between the two drugs was broken at pH 1 at this temperature and the entire drug was available. On the other hand the availability of losartan at pH 4 and 9 was high while it was not available at pH 1 and 7.4. The availability of atorvastatin was maximum in simulated gastric juice as compared to buffer of pH 7.4 and 9. This high availability of one drug in presence of other is attributed to the formation of a charge-transfer complex, which was stable at elevated temperatures, except at 60 degrees C in pH 1.
Arayne
M Saeed
MS
Department of Chemistry, University of Karachi, Karachi-75270, Pakistan. arrayne@gawab.com
Sultana
Najma
N
Haroon
Urooj
U
Qureshi
Faiza
F
Ali
Syed Asif
SA
D047228:Angiotensin II Type 1 Receptor Blockers / Q000032:analysis / Q000737:chemistry*; D000069059:Atorvastatin; D004347:Drug Interactions; D006538:Heptanoic Acids / Q000032:analysis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000032:analysis / Q000737:chemistry*; D019808:Losartan / Q000032:analysis / Q000737:chemistry*; D008956:Models, Chemical; D011758:Pyrroles / Q000032:analysis / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D019808:Losartan