PHARMACOKINETIC AND PHARMACODYNAMIC PROPERTIES AND THERAPEUTIC USE OF BUNAZOSIN IN HYPERTENSION - A REVIEW

Bunazosin (GAS 52712-76-2), a quinazoline derivative, selectively blocks alpha(1)-receptors. In addition to its potent antihypertensive property, beneficial effects on lipid metabolism, glucose metabolism, and vascular smooth muscle cell proliferation, it can be used in the presence of concomitant diseases, such as obstructive bronchitis, chronic renal insufficiency, peripheral arterial occlusive disease, and diabetes mellitus. In its extended-release formulation (bunazosin retard), if is generally a well-tolerated alpha(1)-blocker when compared to other agents in its class. Pharmacokinetic studies in normotensive volunteers showed that plasma peak concentration (C-max) of bunazosin retard and bioavailability were approximately 50 % and SI %, respectively of the values of the standard non-retarded formulation. Bunazosin is metabolized mainly in the liver and urine excretion accounts far only IO % of unchanged bunazosin. Following oral administration of 6 mg bunazosin retard to healthy volunteers, C-max was 15 ng/ml, time to reach peak level (t(max)) was 4 h and elimination half life ,;vas about 12 h. Bunazosin retard has shown C-max and area under the concentration-time curve (AUG) to be linearly related to the dose between 3 and 18 mg (r = 0.8). As expected, patients with impaired hepatic functions have shown an increase it? AUG, C-max and elimination half live values The hemodynamic effects of bunazosin are due to arterial vasodilatation, reduced peripheral vascular resistance and cardiac afterload with moderate increase of cardiac output. Bunazosin was shown to decrease the systolic and diastolic blood pressure without a reflex tachycardia In addition to its hypotensive effects bunazosin significantly, ina eased the effective renal blood flow (by 34 %) and creatinine clearance (by 37 %) in patients,with essential hypertension. In patients with impaired renal function bunazosin exhibits better increase in the effective renal plasma flow and glomerular filtration rate when compared to other alpha(1)-blockers (e.g. prazosin). Results of double-blind, randomized trials in 343 hypertensive patients showed bunazosin to be a equipotent hypotensive agent without multiple titration as usually necessary for other a-blockers. Diastolic blood pressure was normalized (less than or equal to 90 mmHg) or reduced by at least 10 mmHg ii? 47 % and 46 % of patients, respectively.