Clinical pharmacology and pharmacokinetics of prizidilol in hypertensive patients.
We evaluated the clinical pharmacology of prizidilol, a compound with vasodilator and beta-blocking properties, in 12 hypertensive patients with normal renal function. A single dose of 600 mg prizidilol was given orally and blood samples were withdrawn at intervals for high-performance liquid chromatography assay. Blood pressure and heart rate were recorded every hour in supine and standing positions. A nitroglycerin test was performed at the 2nd, 4th, and 6th h for evaluation of cardiac beta-adrenoceptor activity. Results were compared with those after placebo intake the day before. Prizidilol produced a significant decrease in supine systolic and diastolic blood pressures (-22 and -24%, respectively), with a maximum effect 5 h after intake. Blood pressure changes were not different in slow and fast acetylators, suggesting that the acetylated metabolites were active. Heart rate decreased slightly but significantly during the first 2 h, but was similar to control levels thereafter. However, the nitroglycerin test data suggested a prolonged blockade of beta-adrenoceptor activity. Pharmacokinetics showed large variations among patients; several peaks were observed on the curves, indicating irregular absorption. The apparent plasma elimination half-life was 4.4 +/- 0.4 h. Total body clearance was high despite a very low renal clearance, indicating that the drug was eliminated mainly by the metabolic or intestinal route. No significant correlations were found among plasma concentration, blood pressure, and heart rate. In conclusion, prizidilol is a potent antihypertensive drug having equilibrated vasodilator and beta-blocking effects. The pharmacokinetic data suggest a first-pass effect and elimination by extra-renal routes.
D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011187:Posture; D011724:Pyridazines / Q000097:blood / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000097:blood / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D011724:Pyridazines; D014665:Vasodilator Agents; C024293:prizidilol