Ro 31-1118, a new cardioselective beta-adrenoceptor antagonist. Pharmacokinetics and effects on heart rate and blood pressure in mild hypertensives.
Five patients with mild hypertension were given single oral doses of Ro 31-1118 (10,20,40, and 80 mg) and placebo in a randomized, double-blind, within-patient study. Plasma concentrations of Ro 31-1118 and supine, standing, exercise, and post-exercise heart rates and blood pressures were measured before and at regular intervals after drug administration. The pharmacokinetic data were consistent with a one-compartment model with first-order absorption and a variable time lag. Peak plasma concentrations and area under curve were linearly related to dose, whereas time to peak concentration, half-time, clearance and apparent volume of distribution were dose-independent. There was a reduction in exercise and post-exercise heart rate of approximately 10% after 10 mg and 20 mg Ro 31-1118, and of approximately 15% after 40 mg and 80 mg. At all doses standing systolic blood pressure was reduced by approximately 5%. A similar fall was seen in exercise and post-exercise systolic blood pressures. There was no substantial effect of Ro 31-1118 on supine or standing heart rates nor on diastolic blood pressure. No adverse effects were reported. It is concluded that Ro 31-1118 has linear pharmacokinetics over the dose range 10-80 mg, and has a weak antihypertensive effect when administered in single doses to patients with mild hypertension.
Jamieson
M
M
Petrie
J C
JC
Webster
J
J
Miller
A
A
Harris
R I
RI
Francis
R J
RJ
D000042:Absorption; D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000378:metabolism* / Q000627:therapeutic use; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D050198:Phenoxypropanolamines; D005082:Physical Exertion; D011187:Posture; D011412:Propanolamines / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D011897:Random Allocation; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D050198:Phenoxypropanolamines; D011412:Propanolamines; C045426:flusoxolol