Population dose versus response of betaxolol and atenolol: a comparison of potency and variability.
The dose-response curves of betaxolol and atenolol were compared in 140 patients with mild to moderate essential hypertension. Patients with a supine diastolic blood pressure of 95 to 115 mm Hg at the end of a 4-week single-blind placebo washout phase were randomized (double-blind) to receive either betaxolol or atenolol in a dose-escalation manner. The dose (5 mg, 10 mg, and 20 mg betaxolol; 25 mg, 50 mg, and 100 mg atenolol) was increased if the supine diastolic blood pressure remained greater than 90 mm Hg after 4 weeks at each level. The final dose in the escalation phase was continued for an additional 12 weeks and then followed by a 2-week placebo phase. The data were analyzed with a population model using the program NONMEM (nonlinear mixed effects model). Atenolol exhibited a graded dose-response curve, whereas the lowest dose of betaxolol produced maximum or near-maximum effect. The estimated maximum effect (drug plus possibly unmeasured placebo effect) was similar for both treatments, about 13 mm Hg (95% confidence interval, 10 to 15 mm Hg). A trend toward less interindividual variability (coefficient of variation) was apparent for betaxolol compared to atenolol, 19% (95% confidence interval, 0% to 29%) versus 31% (95% confidence interval, 0% to 47%). The intraindividual variability (standard deviation) in supine diastolic blood pressure, 5.9 mm Hg (95% confidence interval, 5.2 to 6.5 mm Hg), did not differ significantly between drugs despite significantly greater intraindividual variability (coefficient of variation) in atenolol concentrations, 62% (95% confidence interval, 48% to 73%) versus 26% (95% confidence interval, 22% to 29%) for betaxolol.
Sambol
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Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
Sheiner
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LB
D000293:Adolescent; D000328:Adult; D000368:Aged; D001262:Atenolol / Q000097:blood / Q000494:pharmacology*; D015784:Betaxolol / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos
D010919:Placebos; D001262:Atenolol; D015784:Betaxolol