Journal List > J Korean Soc Clin Pharmacol Ther > v.21(2) > 1055135

Kim, Lim, Cho, Ghim, Choe, Jung, and Bae: Comparison of Pharmacokinetic Characteristics and Safety Between JW Amlodipine® Tablet 5 mg and Novarsc® Tablet 5 mg in Healthy Male Volunteers

Abstract

Background:

Amlodipine is a third-generation dihydropyridine calcium channel blocker, which has proven to be a useful drug against hypertension or angina.

Methods:

This randomized, open-label, two-period, two-treatment, single-dose, crossover study was conducted in twenty healthy male volunteers. Subjects were administered 5 mg of the test or reference formulation. After 2-week washout period, the other formulation was administered. Blood samples were collected up to 144 hours after drug administration, and plasma amlodipine concentrations were determined by validated liquid chromatography-tandem mass spectrometry. Drug safety was assessed using measurement of vital signs, physical examinations, laboratory test, electrocardiograms, and adverse event monitoring.

Results:

All subjects were completed this study. The geometric mean ratios of Cmax and AUClast were 1.078 (90 % CI, 0.968 - 1.200) and 1.095 (90 % CI, 1.011 - 1.186), respectively. There were no serious adverse events were reported by both formulations.

Conclusion:

This study showed the test and reference formulations had similar pharmacokinetics and safety profiles.

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Figure 1.
Plasma concentration (mean and standard deviation) time curves of amlodipine after a single oral administration of the reference and test formulations.
jkscpt-21-95f1.tif
Figure 2.
Individual profiles of amlodipine after a single oral administration of the test and reference formulations.
jkscpt-21-95f2.tif
Figure 3.
Mean (SD) Systolic (upper) and diastolic blood pressure (lower) after a single oral administration of the test and reference amlodipine 5 mg formulations.
jkscpt-21-95f3.tif
Table 1.
Demographic characteristics of enrolled subjects
Group Age (yr) Weight (kg) Height (cm)
RT (n=10) 24.5 ± 2.88 70.4 ± 10.9 171.8 ± 8.38
TR (n=10) 24.8 ± 4.10 70.8 ± 7.30 174.5 ± 5.22
Total 24.7 ± 3.45 70.6 ± 9.02 173.1 ± 6.93
Table 2.
Pharmacokinetic parameters following administration of the test and reference formulations (n=20)
Test (n=20)
Reference (n=20)
Mean SD CV % Mean SD CV %
AUClast (ng·h×mk-1) 130.03 60.05 46.18 124.01 61.15 49.31
AUCinf (ng·h×ml-1) 149.28 68.00 45.55 141.80 70.53 49.74
Cmax (ng×ml-1) 3.54 1.22 34.52 3.28 1.36 41.54
t1/2β(h) 46.42 12.55 27.04 45.55 14.96 32.84
tmax* (h) 6.00 (2.00, 11.97) 7.99 (3.97, 11.98)

Mean: arithmetic mean. SD: standard deviation. CV %: coefficient of variation = (SD/mean) × 100. *Data are presented as median (min, max). Trademark: Novalopine® 5 mg (JW Pharmaceutical). Trademark: Norvasc® 5 mg (Pfizer).

Table 3.
Bioequivalence assessment of the test and reference formulations
Geometric mean
Geometric Mean Ratio (90 % Confidence Interval)
Test Reference
AUClast 118.79 110.20 1.078 (0.968-1.200)
Cmax 3.30 3.02 1.095 (1.011-1.186)

Trademark: Novalopine® 5 mg (JW Pharmaceutical). Trademark: Norvasc® 5 mg (Pfizer).

Table 4.
Analysis of variance (ANOVA) table for AUClast and Cmax of amlodipine
PK parameters Source df SS MS F p-value
AUClast Sequence 1 0.082 0.082 0.193 0.666
Subject(sequence)
18
7.688
0.427
11.175
<0.001
Period 1 0.095 0.095 2.473 0.133
Formulation 1 0.056 0.056 1.475 0.240
Error
18
0.688
0.038
Cmax Sequence 1 0.110 0.110 0.343 0.565
Subject(sequence)
18
5.743
0.319
14.943
<0.001
Period 1 0.281 0.281 13.138 0.002
Formulation 1 0.082 0.082 3.846 0.066
Error 18 0.384 0.021

Df: degree of freedom. SS: Sum of squares. MS: Mean square. F: F-test statistic.

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