Clinical experience with angiotensin II receptor antagonists.
This series of studies was designed to assess in normal volunteers the relationships between various doses (5, 10, 20, 40, 80, and 120 mg) of the orally active angiotensin II antagonist losartan (DuP 753, MK-954) and their inhibitory effect on the pressure response to a given bolus of angiotensin I or II. It was found that the maximal inhibitory effect was reached with a dose of 80 mg. The minimal dose necessary for maximal efficacy would therefore be expected to be between 40 and 80 mg. The effect lasted for more than 24 h and was related almost exclusively to the circulating levels of the active metabolite EXP3174. It remains to be demonstrated in hypertensive patients that the same dose relationship holds for the antihypertensive effect, but preliminary data already suggest that this is the case.
Brunner
H R
HR
Hypertension Division, University Hospital Center, Lausanne, Switzerland.
Christen
Y
Y
Munafo
A
A
Lee
R J
RJ
Waeber
B
B
Nussberger
J
J
D000284:Administration, Oral; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007275:Injections, Intravenous; D019808:Losartan; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D000803:Angiotensin I; C066026:losartan carboxylic acid; D019808:Losartan