A double-blind, dose-response study of losartan in hypertensive children.
BACKGROUND
The aim of this study was to determine the dose-response relationship for losartan, 2.5 to 100 mg, and to assess the safety and tolerability of losartan in hypertensive children 6 to 16 years of age.


METHODS
This was a multicenter, randomized, double-blind, dose-response study. In Period 1, a total of 175 patients were stratified by weight (<50 kg and >/=50 kg) and randomized to one of three dose groups by stratum (low, 2.5/5.0 mg; middle, 25/50 mg; or high, 50/100 mg) for 3 weeks. The ratio of the three dose levels for both weight strata was 1:10:20. In Period 2, patients in each dose group were randomized to continue the same treatment or placebo washout for 2 additional weeks.


RESULTS
In Period 1, sitting trough diastolic blood pressure (DBP) decreased in a dose-dependent manner (P < .0001). At week 3, changes in DBP from baseline in the low-, middle-, and high-dose groups were -6.0 mm Hg, -11.7 mm Hg, and -12.2 mm Hg, respectively. In Period 2, DBP increased significantly in patients who switched from middle- and high-dose losartan to placebo (mean increase 6.0 mm Hg, P = .003) relative to DBP in patients who remained on active treatment; however, these levels remained stable in those patients who switched from low-dose losartan to placebo (mean increase 1.1 mm Hg, P = .628).


CONCLUSIONS
In hypertensive children 6 to 16 years of age, losartan given once daily reduced blood pressure in a dose-dependent fashion. A once-daily starting dose of losartan, 0.75 mg/kg (maximum 50 mg) effectively lowered DBP within 3 weeks. Losartan up to a dosage of 1.44 mg/kg (maximum 100 mg) once daily is generally well tolerated.
Shahinfar
Shahnaz
S
Merck Research Laboratories, West Point, Pennsylvania, USA. shahnaz_shahinfar@merck.com
Cano
Francisco
F
Soffer
Beth A
BA
Ahmed
Tuli
T
Santoro
Emanuela P
EP
Zhang
Zhongxin
Z
Gleim
Gilbert
G
Miller
Kenneth
K
Vogt
Beth
B
Blumer
Jeffrey
J
Briazgounov
Igor
I
D000293:Adolescent; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male
D000959:Antihypertensive Agents; D019808:Losartan