PENBUTOLOL: NEW~-BLOCKER FROM HOECHST

... Compared with Propranolol in Two StudiesIn 6 volunteers [I], the ~l-blocking potency of penbutolol , anunselective ~-blocker, was compared to that of propranolol in alow dose technique involving continuous infusion of adrenaline(epinephrine) to provide a steady state of ~-agonistic activity .When blood pressure was stabilised, IV propranolol was givenin doses of 10 and 20pg and penbutolol in doses of I and 2pg,and blood pressure was measured for up to I hour after eachdose (or until pretreatment levels were reached). In 4 subjects ,I pg penbutolol was equivalent to 6.43pg of propranolol whilein 2 others the ratio was Ipg penbutolol equals 5.48JIg and .20pg propranolol , respectively.

Six healthy volunteers [2] received penbutolol 10, 20 and40mg, propranolol 160mg and placebo in double-blind cross­over stud ies to determine the effects on heart rate and thecorresponding drug plasma levels. Pulse rates were recordedbefore and during a standard exercise and blood samples takenimmediately after exercise 8 times in the 24-hour periodfollowing dosing .

The dose response curves were parallel throughout the 24hours. with the exception of a slightly faster onset of peakactivity with penbutolol in some patients . Both drugs showedsignificant inhibition of exercise-induced tachycardia at 24hours in comparison with placebo. In most individuals there .wasaclear linear relationship between the Iogarithmof'plasmadrug levels and drug effect for both agents.

[I) Kulkarn i. R.D. et al.: Clinical Pharmacology and Therapeutics 21: 685(Jun 1977)[2)Shand, D.G. et al.: British Journal of Clinical Pharmacology 4: 386P (Jun1977 )

. . . And ClinicalTrial in ArrhvthrniaPenbutolol. a new ~-adrenergic blocking agent, was givenorally to 28 patients with sustained, non-life-threateningcardiac arrhythmias (21 ventricular , 7 supraventr icular). Allpatients started on 4mg tid, with incremental increases to amaximum of 49mg/day. 17 of 21 patients with ventr iculararrhythmia responded, with complete abolition ofarrhythmiasin 14, While3 had satisfactory control. All patients withsupraventricular arrhythmia responded , with complete controlin 5 and partial control in 2. A total of79 % of patients showedsatisfactory or complete response.to I2mg /day. Higher doses .in the other patients did not significantly improve response.Further studies with penbutolol are needed to confirm its valuein managing cardiac arrhythmias .

Gupta , P.S. and Th~ly . L.: Current Therapeuti c Research 21: 638 W ay 1977)

INPHARMA 2nd July. 1977 p7