Is the extrapolated adult dose of fosinopril safe and effective in treating hypertensive children?
We evaluated the efficacy, safety, and dose-response relationship of fosinopril in children aged 6 to 16 years with hypertension or high-normal blood pressure with an associated medical condition requiring treatment. The study was a prospective, double-blind, placebo-controlled trial conducted in 78 clinical sites in the United States, Russia, and Israel. There were 4 phases: a screening phase of 10 days maximum, a 4-week dose-response phase, a placebo withdrawal phase of 2 weeks maximum, and a 52-week open-label safety phase. The primary objective of the dose-response phase was to determine whether low (0.1 mg/kg), medium (0.3 mg/kg), or high (0.6 mg/kg) doses of fosinopril based on established adult dosing affect trough seated systolic blood pressure. During the dose-response phase, all 3 doses were equally effective in lowering systolic blood pressure. During the placebo withdrawal phase, there was an adjusted mean systolic blood pressure increase of 5.2 mm Hg for the placebo group and 1.5 mm Hg for the fosinopril group, a net withdrawal effect of 3.7 mm Hg (P=0.013). Fosinopril was well tolerated; serious adverse events occurred infrequently and were generally not attributed to fosinopril. Because children appear to be more sensitive to lower doses of fosinopril than adults, starting doses for children should be < or =0.1 mg/kg.
Li
Jennifer S
JS
Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Durham, NC 27710, USA. li000001@mc.duke.edu
Berezny
Katherine
K
Kilaru
Rakhi
R
Hazan
Lydie
L
Portman
Ronald
R
Hogg
Ronald
R
Jenkins
Randall D
RD
Kanani
Prapti
P
Cottrill
Carol M
CM
Mattoo
Tej K
TK
Zharkova
Ludmila
L
Kozlova
Ludmila
L
Weisman
Irit
I
Deitchman
David
D
Califf
Robert M
RM
D000293:Adolescent; D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001830:Body Surface Area; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D017328:Fosinopril / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D011355:Prodrugs; D017328:Fosinopril