title: Pharmacokinetic and pharmacodynamic properties and therapeutic use of bunazosin in hypertension. A review.
abstract: Bunazosin (CAS 52712-76-2), a quinazoline derivative, selectively blocks alpha1-receptors. In addition to its potent antihypertensive property, beneficial effects on lipid metabolism, glucose metabolism, 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), it is generally a well-tolerated alpha1-blocker when compared to other agents in its class. Pharmacokinetic studies in normotensive volunteers showed that plasma peak concentration (Cmax) of bunazosin retard and bioavailability were approximately 50% and 81%, respectively, of the values of the standard non-retarded formulation. Bunazosin is metabolized mainly in the liver, and urine excretion accounts for only 10% of unchanged bunazosin. Following oral administration of 6 mg bunazosin retard to healthy volunteers, Cmax was 15 ng/ml, time to reach peak level (tmax) was 4 h and elimination half life was about 12 h. Bunazosin retard has Cmax and area underthe concentration curve (AUC) 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 in AUC, Cmax, and elimination half live values. The hemodynamic effects of bunazosin are due to arterial vasodilation, reduced peripheral vascular resistance and cardiac afterload with moderate increase 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 increased 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 alpha1-blockers (e.g. prazosin). Results of double-blind, randomized trials in 343 hypertensive patients showed bunazosin to be a equipotent hypertensive agent without multiple titration as usually necessary for other alpha-blockers. Diastolic blood pressure was normalized (< or equal 90 mmHg) or reduced by at least 10 mm Hg in 47% and 46% of patients, respectively. Results of two one-year long term studies in more than 600 ¿young¿ and ¿elderly¿ hypertensive patients gave no hint for tachyphylaxia. Bunazosin proved to be superior to prazosin in terms of orthostatic tolerance, as tested with the Schellong test. In conclusion due to its antihypertensive properties, beneficial effects on vascular smooth muscle cells, glucose metabolism , and lipid profile, and the less likelihood of orthostatic hypotension following treatment, bunazosin reard can be considered a useful antihypertensive agent.
authors.affiliation: Sandoz AG, Clinical Research, Nürnberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Weidinger
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D011799:Quinazolines / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; C018176:bunazosin