Non- invasive pharmacologic test performed via rectal administration of Amlodipine, designed to establish vasoreactivity during Pulmonary Arterial Hypertension in patients with Q-postinfarctial remodelling of the LV and Congestive Hearth Failure.

S.I. Kechyn1, N.A. Gorchakova1, S.A. Gladysheva2. 1OO Bohomolets National Medical University, Pharmacology,03055, Ukraine, 2Zaporozhye State Medical University, Industrial and pharmaceutical drug technology,69035, Ukraine

Introduction. Amlodipine is the drug of choice for patients with pulmonary arterial hypertension (PAH) associated with post MI remodulation of the left ventricle and congestive heart failure. Candidates for the treatment by amlodipine are recommended to undergo the acute pharmacologic vasoreactivity test with amlodipine by the right heart catheterization. A positive response is defined as a reduction in mean LAS by 10 - 40 mm Hg. without a significant decrease in the cardiac output. In reality the vasoreactivity test is performed very rarely,only at about 10% of patients with PAH, due to the inaccessibility of the cardiac catheterization in most of the medical institutions. It is known that the absorption of substances from the vials of the rectum through the lower and middle hemorrhoid veins are made directly into the inferior vena cava, which makes it possible to deliver the substance of amlodipine into the pulmonary circulation directly, bypassing the portal system and hepatic biotransformation during the initial circulation.During the oral administration of amlodipine around 90% of substance is metabolized in the liver to form inactive metabolites. Theoretically, the rectal route of administration of amlodipine speeds up the initiation of the hypotensive response .It also enhances the hypotensive response with smaller (than via the oral administration) doses of amlodipine. To perform non-invasive pharmacological test we have developed a polymer-based rectal system with controlled release of substance at 10 mg of amlodipine /30 min.

Purpose. To evaluate the effectiveness of the acute pharmacological test via the rectal administration of amlodipine 10 mg. PAH levels were determined by standard ED at the baseline and 3 hours after the first study at the peak of the hypotensive action of the drug. There were 25 patients selected for the test,all with Coronary Artery Disease, Q - postinfarct left ventricular remodeling and Congestive Heart Failure NYHA class III and PAH WHO class II, which had previously held right heart catheterization with direct determination of the level of PAH. Wilcoxon rank sum test was used for a statistical processing.

Results. 25 patients enrolled in the study had the levels of PAH (interventional examination)at 54.33 + -9.31 mm Hg.The measurement of PAH with the RV dopplerography resulted in 45.80 + -8.23 mm Hg . After the administration of the rectal amlodipine the PAH of 19 patients was measured after 180 min and resulted in :36.20 + -6.02 mmHg (- 21%). The significant reduction in cardiac output was not noted in any of the cases. 6 patients had the reduction of PAH <10%, the rest had an adequate hypotensive response.

Conclusions. Non-invasive pharmacologic test with amlodipine 10 mg rectal suppositories in patients with PAH and CHD associated with Q-postinfarctial remodelling of the LV can be widely used in primary care facilities with the presence of ED to select the patients who can be administered the antihypertensive therapy with amlodipine. Side effects,or any local irritating effects of the use suppositories with controlled release of thesubstance of amlodipine were not detected.