Remikiren (Ro 42-5892)--an orally active renin inhibitor in essential hypertension. Effects on blood pressure and the renin-angiotensin-aldosterone system.
Remikiren (Ro 42-5892) is a new orally active renin inhibitor with high potency and specificity in vitro. In the present study, the drug was given in a short-term study in patients with essential hypertension, either as monotherapy or with added hydrochlorothiazide. Following a wash-out period of at least 3 weeks and then 8 days of single-blind placebo, 29 patients with essential hypertension were given remikiren 600 mg orally for 8 days. After 4 days of remikiren, hydrochlorothiazide 12.5 mg or 25 mg or placebo was added in double-blind fashion for the last 4 days. There were no significant changes in blood pressure in patients given remikiren alone. In patients given additional hydrochlorothiazide for 4 days, a marked reduction in blood pressure was observed. Remikiren effectively inhibited the plasma renin activity 24 h post-dose, whereas angiotensin II was reduced only during the first hours after drug administration. It is concluded that remikiren is orally effective. Its antihypertensive effect during short-term administration was not significant, but when given with a diuretic, a marked potentiation occurred. Further studies are needed to establish the long-term effects of remikiren alone and in combination therapy.
Himmelmann
A
A
Department of Medicine, Ostra Hospital, Göteborg University, Sweden.
Bergbrant
A
A
Svensson
A
A
Hansson
L
L
Aurell
M
M
D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D004232:Diuretics; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use; D000092502:Renin Inhibitors
D000959:Antihypertensive Agents; D004232:Diuretics; D004791:Enzyme Inhibitors; D006852:Hydrochlorothiazide; D007093:Imidazoles; D012083:Renin; D049993:Sodium Chloride Symporter Inhibitors; D000092502:Renin Inhibitors; C065581:remikiren