Interactions between cilazapril and propranolol in man; plasma drug concentrations, hormone and enzyme responses, haemodynamics, agonist dose-effect curves and baroreceptor reflex.
1. The pharmacokinetics, hormonal and haemodynamic responses at rest and during challenges with angiotensin I (blood pressure), isoprenaline (heart rate), and noradrenaline (blood pressure) were investigated in six healthy male volunteers following a 1 week treatment with placebo, propranolol (120 mg day-1), cilazapril (2, 5 mg day-1), and a combination of both in a double-blind cross-over design. 2. Both drugs reduced systolic and diastolic blood pressure by about 7 mm Hg as compared with placebo. After coadministration, this drop in blood pressure was doubled and lasted longer than after the administration of the individual components. 3. Following cilazapril, a pronounced increase in plasma renin activity (PRA) was found (factor approximately 10 at drug peak concentrations). Coadministration of both drugs resulted only in a moderate increase in the PRA (factor approximately 3). Significant changes in plasma catecholamines were not observed. 4. Propranolol shifted the isoprenaline dose-effect curve to the right, and cilazapril that of angiotensin I, irrespective of the presence of the other drug. Cilazapril tended to shift the noradrenaline dose-effect curve somewhat to the right. 5. The gain of the baroreceptor reflex (angiotensin-stimulation) was not influenced by cilazapril but was lowered by propranolol, irrespective of the presence of the ACE inhibitor. 6. Except for a statistically not significant decrease in the peak concentrations of each drug during the combined therapy, a pharmacokinetic interaction between the two drugs was not found.
Belz
G G
GG
Zentrum für Kardiovaskuläre Pharmacologie GmbH., Weisbaden, FRG.
Essig
J
J
Kleinbloesem
C H
CH
Hoogkamer
J F
JF
Wiegand
U W
UW
Wellstein
A
A
D000328:Adult; D000803:Angiotensin I / Q000097:blood / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects*; D011433:Propranolol / Q000097:blood / Q000494:pharmacology*; D011724:Pyridazines / Q000097:blood / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D000804:Angiotensin II; D017315:Cilazapril; D000803:Angiotensin I; D011433:Propranolol; D012083:Renin; D007545:Isoproterenol; D009638:Norepinephrine