The effects of time and dose on the relative beta 1‐ and beta 2‐ adrenoceptor antagonism of betaxolol and atenolol.

Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 40 mg (B40), 80 mg (B80); atenolol 50 mg (A50), 200 mg (A200); or placebo (PL). Measurements of beta 1-adrenoceptor blockade (reduction of exercise heart rate) and of beta 2-adrenoceptor blockade (attenuation of isoprenaline responses) were made at baseline, and at 2, 4, 6, 8 and 24 h after drug ingestion. 2. Mean values for Cmax and tmax were as follows: B10 (33 ng ml-1, 3.7 h), B40 (84 ng ml-1, 4.0 h), B80 (179 ng ml-1, 3.7 h); A50 (261 ng ml-1, 2.7 h), A200 (1369 ng ml-1, 2.0 h). 3. Reduction of exercise heart rate (EHR) occurred in dose-dependent fashion up to a ceiling at B40 (as % reduction c.f. placebo, at peak and 24 h): B10 16.2 to 10.2%, B40 27.1 to 16.2%, B80 27.0 to 18.7%; A50 20.9 to 9.1%, A200 28.8 to 15.8%. There were also dose-related increases in beta 2-adrenoceptor antagonism (IT100 dose ratios, at peak and 24 h): B10 2.1 to 1.2, B40 4.7 to 2.6, B80 6.0 to 4.7; A50 2.0 to 1.2, A200 4.7 to 1.8. There were similar trends for attenuation of heart rate and DBP responses to isoprenaline. 4. Ratios of beta 1:beta 2-adrenoceptor antagonism were calculated (as % reduction EHR divided by IT100 dose ratio); to provide an index of beta 1-adrenoceptor selectivity at peak and 24 h: B10 7.7 to 8.5, B40 5.8 to 6.2, B80 4.5 to 4.0; A50 10.5 to 7.6, A200 6.1 to 8.8.(ABSTRACT TRUNCATED AT 250 WORDS)