In vitro and In vivo Interactions of Diltiazem with Ibuprofen and Naproxen in Aqueous Medium and Rabbits Md. Shah Amran, A.H.M. Rashidul Bari and Md. Amjad Hossain 1 Department of Pharmacy, Faculty of Science, Rajshahi University, Rajshahi-6205, Bangladesh 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Dhaka University, Dhaka-1000, Bangladesh ABSTARCT: A common practice in the medical science is the prescription of multiple drugs at a time, which may sometimes be neither safe nor effective and may be deleterious. The present study was aimed to evaluate such a combination of diltiazem with ibuprofen and naproxen. The invitro interaction of diltiazem with ibuprofen and naproxen has been studied at room temperature and at different pH in the aqueous medium by spectroscopic and conductometric methods, and the invivo study was done in the rabbit by measuring blood pressure using a mercury manometer. It has been found that diltiazem formed stable 1 : 1 complexes with ibuprofen and naproxen along with some intermediates. The Ardon’s spectrophotometric method was employed to confirm the formation of 1 : 1 complex and for the calculation of the stability constants. The invivo study was carried out to evaluate the influence of ibuprofen and naproxen on the antihypertensive activity of diltiazem in the rabbit. Concurrent administration of ibuprofen and naproxen with diltizem did not make any significant change in the antihypertensive activity of diltiazem. It is thus inferred that co-administration of diltiazem with ibuprofen and naproxen may be considered as safe and effective. Key words: Drug interaction, complexation, co-administration, diltiazem, naproxen, ibuprofen, stability constant INTRODUCTION Diltiazem hydrochloride is an important calcium channel blocker. Clinically it is used to treat cardiovascular diseases such as angina pectoris, hypertension and cardiac arrhythmias. Ibuprofen and naproxen are nonsteroidal anti-inflammatory agents. Clinically they are used for the treatment of rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute gout, acute musculoskeletal pains, mild to moderate pian such as dysmenorrhea and migrane. Hamman et al. 1 studied the cardiodepressant actions of diltiazem with propranolol in dogs. They observed that when given alone diltiazem increased cardiac output and PR Correspondence to: Md. Amjad Hossain Tel: 88-02--9661920-73, Extn. 8130, 8135 E-mail: amjad@univdhaka.edu Dhaka Univ. J. Pharm. Sci. 5(1-2): 25-28, 2006 (June-December) interval while decreasing mean arterial pressure, heart rate and systemic vascular resistance. Propranolol alone decreased cardiac output and heart rate while increasing vascular resistance. But a combination therapy resulted in a depression upto levels similar to those achieved with propranolol alone and a decrease in mean arterial pressure upto levels achieved with diltiazem alone. PR interval increased beyond the duration produced by either drug given alone. It was thus inferred that there was no apparaent interaction between diltiazem and propranolol. Saseen et al. 2 studied the effect of nifedipine on diltiazem/verapamil and showed that combination therapy exhibited a greater antihyper- tensive activity than nifedipine alone. The aim of the present study was to evaluate the invitro and invivo effcets of ibuprofen and naproxen on the physicochemical and therapeutic activity of