Clinic blood pressure responses to two amlodipine salt formulations, adipate and besylate, in adult Korean patients with mild to moderate hypertension: a multicenter, randomized, double-blind, parallel-group, 8-week comparison.
BACKGROUND
The commercially available formulation of amlodipine is conjugated with besylate salt to increase water solubility. Recently, a new amlodipine salt formulation has been developed in which the free base of amlodipine is conjugated with a chemically different salt, adipate.


OBJECTIVE
The goal of this study was to compare the antihypertensive effect and tolerability of amlodipine adipate with those of amlodipine besylate in patients with mild to moderate hypertension.


METHODS
This was a multicenter, randomized, doubleblind, parallel-group study in which patients received 8 weeks of treatment with either amlodipine adipate or amlodipine besylate. The primary efficacy variable was noninferiority of the difference in mean changes from baseline in trough diastolic blood pressure (DBP) after 8 weeks of treatment. Secondary efficacy variables included mean changes in DBP, systolic blood pressure (SBP), and response rate (defined as the proportion of patients whose DBP was <90 mm Hg or whose DBP had decreased from baseline by > or =10 mm Hg). The incidence of adverse events (AEs) was also assessed.


RESULTS
Two hundred eleven patients were randomly assigned to receive amlodipine adipate (n = 106) or amlodipine besylate (n = 105). Study patients were primarily female (54.5%), with a mean (SD) age of 52.2 (9.6) years and a mean body weight of 67.1 (10.2) kg; there were no between-group differences in demographic profiles. After 4 weeks of randomized treatment, 58 (27.5%) patients (29 [27.4%] amlodipine adipate, 29 [27.6%] amlodipine besylate) had not achieved a mean DBP <90 mm Hg, and their dose was doubled. Mean DBP changes at 8 weeks were -15.2 (7.3) mm Hg in the amlodipine adipate group and -14.2 (7.4) mm Hg in the amlodipine besylate group (P = NS). Because the 95% CI for the difference in mean DBP changes between groups (-0.53 to 2.55) was within the prespecified lower limit (-4 mm Hg), amlodipine adipate was considered noninferior to amlodipine besylate. Mean SBP changes were -24.9 (12.1) mm Hg in the amlodipine adipate group and -22.0 (14.7) mm Hg in the amlodipine besylate group (P = NS). The response rates were 92.0% for amlodipine adipate and 95.4% for amlodipine besylate (P = NS). The overall incidence of clinical AEs was 20.8% in the amlodipine adipate group and 25.7% in the amlodipine besylate group (P = NS). Drug-related clinical AEs occurred in 5.7% and 12.4% of patients in the respective treatment groups (P = NS). Serum uric acid levels decreased significantly from base-line in both groups (P < 0.001).


CONCLUSIONS
Eight weeks of treatment with amlodipine adipate produced significant reductions from baseline in blood pressure in these patients with mild to moderate hypertension. The efficacy of amlodipine adipate was not inferior to that of amlodipine besylate. Tolerability was comparable between the 2 treatment groups.
Lee
Hae-Young
HY
Department of Internal Medicine, Seoul National University College of Medicine, Korea. ohbhmed@snu.ac.kr
Kang
Hyun-Jae
HJ
Koo
Bon-Kwon
BK
Oh
Byung-Hee
BH
Heung-Sun
Kang
K
Kim
Kee-Sik
KS
Seo
Hong Seog
HS
Ro
Young Moo
YM
Kang
Jin-Ho
JH
Woong
Choi Jae
CJ
Joo
Seung-Jae
SJ
Kim
Moo Hyun
MH
Joon-Han
Shin
S
Yoon
Junghan
J
Park
Seong-Hoon
SH
Jin-Ok
Jeong
J
Ju
Ahn Kyoung
AK
Chong-Yun
Rhim
R
Yeon
Kyu Jeong
KJ
Park
Kyung Mi
KM
Lim
Dong Kwon
DK
Park
So Youn
SY
D000272:Adipates / Q000737:chemistry*; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002214:Capsules; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005483:Flushing / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007723:Korea; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011537:Pruritus / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome
D000272:Adipates; D000959:Antihypertensive Agents; D002214:Capsules; D017311:Amlodipine; C029900:adipic acid