Pharmacokinetic and pharmacodynamic interactions between the ACE inhibitor cilazapril and beta-adrenoceptor antagonist propranolol in healthy subjects and in hypertensive patients.
1. Six healthy subjects received cilazapril (2.5 mg once daily), propranolol (120 mg once daily), the combination of both and placebo for a period of 1 week each (wash-out phase 1 week). 2. Propranolol and cilazapril reduced systolic and diastolic blood pressure (BP) by 7 mm Hg at peak when compared with placebo. However after the combination, this reduction was more than doubled (18 mm Hg) and lasted longer. 3. There was a trend to lower and later peak concentrations for both drugs after administration of the combination. No clinically relevant pharmacokinetic interactions between cilazapril and propranolol were found. 4. The effects on blood pressure were confirmed in hypertensive patients (BP diastolic greater than 95 mm Hg). Thirteen patients were randomly allocated cilazapril (2.5 mg day-1) or propranolol (120 mg day-1] as part of a cross-over design. This was then followed by the combination. All treatment periods were of 3 weeks duration and all measurements were done 2 h after drug administration. 5. Cilazapril lowered the median sitting diastolic BP by 8 mm Hg, and propranolol by 9 mm Hg, whereas the combination reduced the diastolic BP by 19 mm Hg. 6. The results of these studies, attempting to elucidate drug-drug interactions, showed that combined use of propranolol and cilazapril resulted in a more pronounced and longer lasting blood pressure reduction, in healthy subjects and in patients with hypertension.
Belz
G G
GG
Zentrum für Kardiovaskuläre Pharmackologie, Ze Ka Pha GmbH, Wiesbaden, Federal Republic of Germany.
Essig
J
J
Erb
K
K
Breithaupt
K
K
Hoogkamer
J F
JF
Kneer
J
J
Kleinbloesem
C H
CH
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000493:pharmacokinetics / Q000494:pharmacology*; D011724:Pyridazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011897:Random Allocation; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D011433:Propranolol; D012083:Renin