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The SynerGISm of Diltiazem and Nifedipine in Their Antihypertensive Functions in the Animal Model and the Case of Coadministration of Ketotifen Fumerate and Potassium Nitrate with Them

Md Shah Amran
Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi-6205, Bangladesh

Md Rahatuzzamn
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh

Md Amjad Hossain
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh

Abstract/ Executive Summary:

An in vivo study has been carried out to evaluate the synergism of diltiazem and nifedipine on the antihypertensive activity and the effect of ketotifen fumerate and potassium nitrate on this phenomenon of synergism in rabbit. It has been found that the lowering of blood pressure by concurrent administration of diltiazem and nifedipine was not equal to the sum of lowering of blood pressure by individual drug. Concurrent administration of ketotifen fumerate and potassium nitrate with diltiazem or with nifedipine did not make a significant change on the antihypertensive activity of diltiazem or nifedipine. Further considerations and monitoring are to be practiced during concurrent therapy of diltiazem and nifedipine to avoid untoward pharmacological and therapeutic actions related to drug- interactions but coadministration of ketotifen fumerate and potassium nitrate with either diltiazem or nifedipine might be regarded as safe and effective.

Keywords: In vivo, Antihypertensive activity, Nifedipine, Diltiazem, Ketotifen fumerate, Potassium nitrate, Coadministration

Location: Dhaka

Start Date: 01-01-2000

End Date: 30-06-2001

Program Area: Knowledge Management

Commodity: Heavy metal

Objectives:

To evaluate the synergism of diltiazem and nifedipine, and the effect of ketotifen fumerate and potassium nitrate on hypotensive activity of diltiazem and nifedipine and thus to infer about the fate of combined drug therapy of these drugs.

Methodology:

A mercury manometer was used for the measurement of blood pressure of the rabbit. Sterile and disposable plastic syringes were used to inject the drugs in the solution form. Diltiazem HCI, ketotifen fumerate were obtained from Beximco Pharmaceuticals l.td., (Bangladesh). ACME Laboratories Ltd. (Bangladesh), kindly supplied nifedipine. Potassium nitrate was of analytical grade (BDH, England) and Heparin was purchased from Leo Pharmaceutical products, Denmark. Phenobarbital injection was purchased from Jayson Pharmaceuticals Ltd., (Bangladesh). Forty rabbits were used for determination of blood pressure or antihypertensive activity. Body weight of rabbit was 2 ± 0.1 kg. Animals were obtained from International Centre for Diarrheal Disease Research, Bangladesh (ICDDR, B). The antihypertensive activity of diltiazem and nifedipine, and the combinations of ketotifen fumerate and potassium nitrate in rabbits was measured directly by a mercury manometer. Forty adult healthy rabbits were used as experimental animals. They were kept at rest for 7 days with normal diets. Thirty- five rabbits were divided into 7 groups each having 5 (marked as group I - VIII) and the rest five as control (control group). They were fasted overnight before drug administration. Each rabbit was sedated by injecting Phenobarbital sodium (30 mg/ kg, intraperitonially, i.p.). The common carotid artery was cannulated and connected directly to the mercury manometer. The femoral vein was also cannulated and used for drug administration. Diltiazem HCI (1 mg/ kg) was injected through the femoral vein to each animal (group I) and the .suosequent effect on blood pressure was noted. Then nifedipine was injected in each rabbit at the same dose (1 mg/ Kg) in the similar manner (group II). The fall in the blood pressure was recorded. The combined doses {(diltiazem+ nifedipine (group Ill), diltiazern- ketotifen fumerate (group IV), diltiazern- potassium nitrate (group V) and (nifecipine- ketotiten fumerate (group VI), nifedipine+ potassium nitrate (group VII)) were injected respectively in all groups of animals and the subsequent effects on the blood pressure were recorded. Data are shown as mean ± SEM. The variation in blood pressure was analyzed by students 't' test. A probability value of 0.05 (p<0.05) was defined to be significant. Data were analyzed by the software graphpad Prism.

Source of Information: JOURNAL OF BIO-SCIENCE, THE INSTITUTE OF BIOLOGICAL SCIENCES RAJSHAHI UNIVERSITY, Vol. 14, 2006, pp. 61-67, ISSN 1023–8654.

Article Link (Online Journal):

Funding Source:

Total Budget (Tk.) :

Achievement/Findings:

It has been found that the lowering of blood pressure by concurrent administration of diltiazem and nifedipine was not equal to the sum of lowering of blood pressure by individual drug. Concurrent administration of ketotifen fumerate and potassium nitrate with diltiazem or with nifedipine did not make a significant change on the antihypertensive activity of diltiazem or nifedipineIt can be inferred that great care and monitoring should be practiced during coadministration of diltiazem with nifedipine. Ketotifen fumerate and potassium nitrate can be coadministered either with diltiazem or nifedipine without fear of any interaction or adverse effects.

Knowledge Management: Journal