Yo Han Kim; Hyeong-Seok Lim; Sang-Heon Cho; Jong-Lyul Ghim; Sangmin Choe; Jin Ah Jung; Kyun-Seop Bae

doi:10.12793/jkscpt.2013.21.2.95

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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

Original Article

J Korean Soc Clin Pharmacol Ther 2013;21(2):95-103.

Published online: 11 January 2013

DOI: https://doi.org/10.12793/jkscpt.2013.21.2.95

Comparison of Pharmacokinetic Characteristics and Safety Between JW Amlodipine^® Tablet 5 mg and Novarsc^® Tablet 5 mg in Healthy Male Volunteers

Yo Han Kim, MD^1,², Hyeong-Seok Lim, MD, PhD^1,², Sang-Heon Cho, MD, PhD³, Jong-Lyul Ghim, MD, PhD⁴, Sangmin Choe, MD, PhD⁵, Jin Ah Jung, MD, PhD⁶, Kyun-Seop Bae, MD, PhD^1,²

¹Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Korea

²University of Ulsan College of Medicine, Inha University Hospital, Inha University Scull of Medicine, Incheon, Korea

³Department of Clinical Pharmacology, Inha University Hospital, Inha University Scull of Medicine, Incheon, Korea

⁴Department of Clinical Pharmacology, Busan Paik Hospital, Busan, Korea

⁵Clinical Trials Center, Pusan National University Hospital, Busan, Korea

⁶Clinical Trial Center, Samsung Medical Center, Seoul, Korea

E-mail: ksbae@amc.seoul.kr

Received 31 July 20137 October 2013 Accepted 10 October 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 C_max and AUC_last 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.

Keywords: Amlodipine, Pharmacokinetics, Safety, Healthy volunteers

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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.

Figure 2.

Individual profiles of amlodipine after a single oral administration of the test and reference formulations.

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.

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 %
AUC_last (ng·h×mk^-1)	130.03	60.05	46.18	124.01	61.15	49.31
AUC_inf (ng·h×ml^-1)	149.28	68.00	45.55	141.80	70.53	49.74
C_max (ng×ml^-1)	3.54	1.22	34.52	3.28	1.36	41.54
t_1/2β(h)	46.42	12.55	27.04	45.55	14.96	32.84
t_max* (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^‡	Geometric Mean Ratio (90 % Confidence Interval)
AUC_last	118.79	110.20	1.078 (0.968-1.200)
C_max	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 AUC_last and C_max 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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