An investigation into the cardiac and pulmonary beta-adrenoceptor blocking activity of ICI 66,082 in man.

1 Oral ICI 66,082 (200 mg) or water (control treatment) were each administered to six healthy volunteers. 2 The heart rate (HR) and peak flow rate (PFR) were measured at rest and during vigorous exercise before and at intervals up to 24 h after each treatment. 3 ICI 66,082 produced significant reductions in exercise HR at all times compared with the changes after the control treatment (P less than 0.001), whereas with resting HR, corresponding significant reductions only occurred at 2,3 and 4 h (P less than 0.05). 4 Although there was no change in resting PFR, significant reductions in exercise PFR, compared with the changes after the control treatment, occurred at all times excepting at 2 h after ICI 66,082 (P less than 0.025). 5 The findings are consistent with ICI 66,082 possessing partial cardioselectivity. 6 Plasma levels and renal excretion of the drug were determined. Urinary recovery was variable which, together with the plasma concentration/effect relationships obtained, raise the possibility that ICI 66,082 is metabolized in man.