Prizidilol, a combined vasodilatory and beta-adrenoceptor blocking drug, in primary hypertension. A long-term efficacy, tolerance and pharmacokinetic study.
After an initial placebo period of four weeks 24 patients with primary hypertension were treated with prizidilol, a hydrazinopyridazine derivative with combined vasodilator and non-selective beta-adrenoceptor blocking actions, for a dose titration period of 14 weeks. Prizidilol 200 to 800 mg was given once daily to achieve a target supine diastolic blood pressure (BP) less than 90 mmHg. Supine and standing BP recorded 24-27 h after drug intake decreased from 172 +/- 17/106 +/- 6 mmHg (mean +/- SD) and 167 +/- 18/111 +/- 8 mmHg, respectively, after placebo to 159 +/- 16/99 +/- 8 and 154 +/- 18/101 +/- 9 mmHg after active treatment for six weeks (mean dose 447 mg), and to 154 +/- 16/97 +/- 7 and 148 +/- 14/97 +/- 7 mmHg after treatment for 14 weeks (mean dose 687 mg/day). A slight reduction in HR was seen after treatment for six weeks and in plasma renin activity and urinary methoxycatecholamine excretion after treatment for 14 weeks. A sustained decrease in BP was observed for 10 h after prizidilol 800 mg (n = 9), with a maximum antihypertensive effect (mean reduction in supine BP 33/18 mmHg) 2.5 h after dosing, which coincided with the mean peak plasma concentration. The plasma elimination half-life of the drug was 3.9 h (range 2.0-8.9 h). Changing to a twice daily regimen in 17 patients (mean daily dose 748 mg at six months) did not produce any further reduction in the BP (recorded 12-15 h after dosing) as compared to the once daily regimen at 14 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
D000107:Acetylation; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011724:Pyridazines / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D000974:Antibodies, Antinuclear; D011724:Pyridazines; D014665:Vasodilator Agents; C024293:prizidilol