D. Molotyagin

The Kharkov National Medical University, Ukraine

Experimental research of allergenic effect of

coformulated antihypertensive drug

Optimizing the treatment of arterial hypertension is being improved alongside with the creation of new antihypertensive drugs in the form of fixed combinations. It is an obligation to study the innocuity of therapeutic combinations of diverse complexities, even for those that consist of well-known drugs, since their use in combination does not eliminate the danger of general toxic effect of separate components. The overall program of the research studies the innocuity of new drugs contains the determination of their allergenic effect.

The aim of the research is to study the allergenic effect of a new coformulated antihypertensive COMBI drug that contains bisoprolol, lisinopril and indapamide.

The experiment was performed on 18 light-colored cavies, weighing from 610 to 700 g, divided into 3 groups: 1st group was used as a control group and received 3% starch mucilage, 2^nd group was given a COMBI drug at the recommended therapeutic dose (8 mg/kg), 3rd group was given a COMBI drug at a dose 10 times bigger than the therapeutic dose (80 mg/kg). Oral and dermal methods of sensitization were used.

Over time of sensitization (on 10th, 15th and 30th day) body weight, body temperature measured in the rectum and on the skin, alongside with intradermal allergy testing were determined and analyzed. On the 30th day the number of eosinophils in the blood and reaction of specific agglomeration of leukocytes (RSAL) and the reaction of alteration of neutrophils (RAN) were determined. In an independent series of experiments on guinea pigs conjunctival sample was set.

Results of the research showed that the sensitization of COMBI drug within the set limits did not cause death of animals: they were moderately agile and feeding activity was intacted. Weight of all animals in all groups has increased during the experiment.

The observed fluctuations in body and skin temperature for animals that were given COMBI drug in two doses cannot be associated with allergenic effect of COMBI drug in terms of a similar change in the control group. During the intradermal test on the 10th, 15th and 30th day of the test using COMBI drug in two doses no irritation phenomena, erythema, infiltration, focal skin ulcerations in all groups were observed.

RSAL showed that the percent of agglomerated leucocytes in experimental groups didn’t exceed the measures of the control group.

RAN, which reflects the degree of allergic degeneration of neutrophils and their intracellular organelles influenced by COMBI drug sensitization in the fixed doses showed absence of sensitizing effect.

The level of eosinophils in the experimental groups did not exceed the measures of the control group. Conjunctival sample data indicated that after 15 minutes, 24 hours and 48 hours since instillation of COMBI drug no hyperemia, infiltration of the lacrimal duct, scleral conjunctiva and mucosa were detected.

Therefore, COMBI drug in the fixed doses along with overlapping sensitization with integral indicators, intradermal samples, diagnostic tests (RSAL, RAN), number of blood eosinophils has no allergenic effect. The absence of specific sensitization is confirmed with the negative conjunctival sample of guinea pigs.