Comparison of Pharmacokinetic Characteristics and the Safety between Amlodipine Maleate Tablet 5 mg and Amlodipine Besylate Tablet 5 mg

Hee Youn Choi; Jae Woo Kim; Hyeong-Seok Lim; Sang-Heon Cho; Jong-Lyul Ghim; Sangmin Choe; Jin Ah Jung; Jonglae Lim; Kyun-Seop Bae

doi:10.0000/jkscpt.2012.20.1.42

Journal List > J Korean Soc Clin Pharmacol Ther > v.20(1) > 1055113

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Choi, Kim, Lim, Cho, Ghim, Choe, Jung, Lim, and Bae: Comparison of Pharmacokinetic Characteristics and the Safety between Amlodipine Maleate Tablet 5 mg and Amlodipine Besylate Tablet 5 mg

Original Article

Journal of Korean Society for Clinical Pharmacology and Therapeutics

Journal of Korean Society for Clinical Pharmacology and Therapeutics 2012; 20(1): 42-50.

Published online: 30 June 2011

DOI: https://doi.org/10.0000/jkscpt.2012.20.1.42

Comparison of Pharmacokinetic Characteristics and the Safety between Amlodipine Maleate Tablet 5 mg and Amlodipine Besylate Tablet 5 mg

Hee Youn Choi^1,², Jae Woo Kim^1,², Hyeong-Seok Lim^1,², Sang-Heon Cho³, Jong-Lyul Ghim⁴, Sangmin Choe⁵, Jin Ah Jung⁶, Jonglae Lim⁷, Kyun-Seop Bae^1,²

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

²University of Ulsan College of Medicine, Korea.

³School of Military Medicine, The First Republic of Korea Army, Korea.

⁴Department of Clinical Pharmacology and Therapeutics, Inje University Pusan Paik Hospital, Pusan, Korea.

⁵Division of Clinical Pharmacology, Clinical Trials Center, Pusan National University Hospital, Korea.

⁶Division of Clinical Pharmacology, Clinical Trial Center, Samsung Medical Center, Korea.

⁷Technical research center, CKD research institute, Chong Kun Dang Pharmaceutical Co, Ltd, Korea.

Corresponding author (ksbae@amc.seoul.kr)

Received 1 December 2011 Revised 7 May 2012 Accepted 12 May 2012

Abstract

Background

Amlodipine is a third-generation dihydropyridine calcium channel blocker for treating hypertension. Though marketed primarily as a besylate salt, there have been some efforts to find other comparable salts. Among them, maleate is the salt that has been considered favorable for many drugs. The aim of this study was to compare the pharmacokinetics, as well as safety and tolerability of amlodipine maleate with amlodipine besylate.

Methods

This study was open, randomized, two-period crossover design investigated in twelve healthy male volunteers over a 144 h period after administrating two forms of amlodipine 5 mg, respectively. Each period was separated with 2 weeks. Plasma concentrations of amlodipine were determined by liquid chromatography-tandem mass spectrometry. Safety profiles were assessed by vital signs, physical examinations, electrocardiograms, laboratory testing and adverse events monitoring.

Results

All subjects were completed this study. Geometric mean ratios (GMRs) of amlodipine maleate/amlodipine besylate of C_max and AUC_last for amlodipine were 0.92 (90 % confidence interval, 0.81 ~ 1.05) and 1.05 (0.96 ~ 1.16), respectively. No serious adverse events were reported, and no clinically relevant changes were observed in safety profiles during this trial.

Conclusion

Pharmacokinetics, tolerability and the safety were comparable between amlodipine maleate and amlodipine besylate in healthy individuals.

Keywords: Amlodipine maleate, Amlodipine besylate, Pharmacokinetics

Figures and Tables

Figure 1

Mean plasma amlodipine concentration-time curves.

Figure 2

Systolic blood pressure (upper), diastolic blood pressure (middle), pulse rate (low). Data are presented as mean ± SD.

Table 1

Characteristics of Enrolled Subjects

^*Mann-Whitney U test.

Table 2

Pharmacokinetic parameters of amlodipine

Table 3

Geometric mean and ratios of primary amlodipine pharmacokinetic parameters for amlodipine maleate and amlodipine besylate and 90% confidence interval limits

^*Geometric mean ratio of amlodipine maleate 5 mg to amlodipine besylate 5 mg; exponentiation of difference between means after log-transformation.

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