Relationships among timolol doses, plasma concentrations and beta‐ adrenoceptor blocking activity

1 We investigated the relationships among dose, plasma concentration and beta‐adrenoceptor blockade after single and repeated doses (0.5‐20 mg) of timolol and placebo in six normal men. 2 Maximal suppression of exercise‐induced tachycardia (bicycle ergometry) was dose‐dependent and greater at 2 than at 6 h after dosing; activity up to 12 h was evident on the last dosing day. 3 Attenuation of exercise‐induced tachycardia was strongly correlated with the timolol dosage over the 0.5 to 5‐10 mg range. 4 A plasma timolol concentration of 27 ng/ml was associated with maximal suppression of exercise‐induced tachycardia. 5 Suppression of exercise‐induced tachycardia and areas under the plasma concentration‐ time curves did not differ significantly on the first and last dosing days.