title: Double-blind crossover study of the interaction between perindopril and amlodipine on blood pressure and hormones related to fluid and electrolyte balance in patients with essential hypertension.
abstract: This study was to investigate the interaction between low doses of perindopril (2 mg daily) and amlodipine (2.5 mg daily) on ambulatory blood pressure (BP), clinic BP, serum angiotensin-converting enzyme (ACE), plasma levels of renin (PRA), angiotensin II (Ang II), aldosterone, and atrial natriuretic peptide (alpha-h ANP) in subjects with essential hypertension. The study design was a parallel, two-period, placebo-controlled, double-blind crossover design, with 11 subjects receiving perindopril and 10 receiving amlodipine during the run-in phase. The addition of amlodipine to perindopril had no effect on ambulatory BP, whereas the addition of perindopril to amlodipine reduced both systolic (P = 0.027) and diastolic (P = 0.049) ambulatory BP. By contrast, the opposite result was obtained for clinic BP at trough, whereby the addition of amlodipine to perindopril reduced erect systolic BP (P = 0.036) and both supine and erect diastolic BP (P = 0.038) whereas the addition of perindopril to amlodipine was without effect. The addition of perindopril to amlodipine decreased serum ACE by 72% and increased PRA two-fold, without change in plasma levels of Ang II, aldosterone or alpha-h ANP. The addition of amlodipine to perindopril increased plasma aldosterone 1.7-fold but did not affect serum ACE, PRA, Ang II, or alpha-h ANP. These interactions between perindopril and amlodipine may have been conditioned by the specific effects of the therapy first given, as well as by the different circumstances of BP measurement (ambulatory vs clinic).
authors.affiliation: Department of Clinical Pharmacology, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: G S
authors.initials: GS
authors.lastname: Stokes
authors.forename: J C
authors.initials: JC
authors.lastname: Monaghan
authors.forename: K
authors.initials: K
authors.lastname: Berman
authors.forename: M
authors.initials: M
authors.lastname: Ryan
authors.forename: D J
authors.initials: DJ
authors.lastname: Campbell
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D020913:Perindopril; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D006728:Hormones; D007211:Indoles; D017311:Amlodipine; D020913:Perindopril