Interaction Studies of ACE Inhibitors with Antidiabetic Drugs

Abstract

Angiotensin converting enzyme (ACE)-inhibitors are effective in patients with mild to moderately severe hypertension, collagen vascular and cardiovascular disease. They are also used in the prevention and treatment of myocardial infarction and in the management of cardiac arrhythmias. Patients with cardiovascular diseases are generally on multiple medicines that’s why it is imperative to study drug–drug interactions of medicines which are commonly taken together in any given case, as combined administration of different medicines can significantly influence the availability of drugs. In the present study we investigated the “in vitro” interactions of ACE inhibitors (enalapril, captopril and lisinopril) with frequently prescribed and co-administered drugs in simulated human body environments. These interactions were monitored by means of UV spectrophotometry and separation technique as RP-HPLC. Prior to start of actual drug interactions, the method of analysis of each drug was established and its various parameters validated for considering its use in testing of drug in vitro as well as in human serum. For this purpose, an attempt was made to develop a number of new HPLC methods for determination of ACE inhibitors (enalapril, captopril and lisinopril) and simultaneously with interacting drugs. These methods were optimized, validated and then successfully employed for the quantitation of enalapril, captopril and lisinopril and selected drugs in interactions studies. As a result, new methods for the quantitation of individual as well as multiple drugs were developed. The interacting drugs selected were antidiabetic drugs (metformin, glibenclamide, glimepride and pioglitazone. Interaction consequences revealed that the availability of enalapril was not affected in presence of antidiabetic drugss whereas the availability of captopril and lisinopril were altered in presence of NIDDMs.