Bioequivalence and Dose Proportionality of Olmesartan Medoxomil Formulations

Sung Kweon Cho; Choon Ok Kim; Su Hyun Yu; Eun Sil Oh; Seong Bok Jang; Yoong Sik Park; Kyunghee Cho; Jae-Yong Chung

doi:10.0000/jkscpt.2012.20.2.145

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Cho, Kim, Yu, Oh, Jang, Park, Cho, and Chung: Bioequivalence and Dose Proportionality of Olmesartan Medoxomil Formulations

Original Article

Journal of Korean Society for Clinical Pharmacology and Therapeutics

Journal of Korean Society for Clinical Pharmacology and Therapeutics 2012; 20(2): 145-154.

Published online: 31 December 2012

DOI: https://doi.org/10.0000/jkscpt.2012.20.2.145

Bioequivalence and Dose Proportionality of Olmesartan Medoxomil Formulations

Sung Kweon Cho¹, Choon Ok Kim¹, Su Hyun Yu¹, Eun Sil Oh¹, Seong Bok Jang², Yoong Sik Park², Kyunghee Cho³, Jae-Yong Chung¹

¹Department of Clinical Pharmacology, Yonsei University College of Medicine, Seoul, Korea.

²Yuhan Corporation, 49-6, Daebang-dong, Dongjak-gu, Seoul, Korea.

³Biocore Corporation, #60-21, Gasan-dong, Geumcheon-gu, Seoul, Korea.

Corresponding author (mekka@snu.ac.kr)

Received 8 October 2012 Revised 13 December 2012 Accepted 17 December 2012

Abstract

Background

Olmesartan medoxomil is an angiotensin II receptor blocker commonly used in hypertension. First objective of this study was to evaluate the bioequivalence of two olmesartan formulations, Olmesartan 20 mg and 40 mg tablet (Yuhan, Pharmaceutical Corp. Seoul, Korea) as test drugs and Olmetec® 20 mg and 40 mg tablet (Daewoong, Pharmaceutical Corp. Seoul, Korea) as reference drugs. Second objective of this study was to evaluate the dose-proportionality of two formulations.

Methods

Two studies (20 mg, 40 mg) were conducted as a randomized, open-label, 2-period, crossover design. Each subject received one 20 mg or 40 mg tablet of the reference or test formulation of olmesartan medoxomil in each study. Blood samples were obtained during the 48-hour period after the dose in each treatment period. Wash-out period was 1 week in each study. Concentrations of olmesartan medoxomil in plasma were analyzed using a liquid chromatography system with tandem mass-spectrometric detection (LC/MS/MS). The primary pharmacokinetic parameters were C_max (maximum concentration) and AUC_t (area under the concentration-time curve from time 0 to the last sampling time).

Results

A total number of 40 healthy male volunteers participated in the study and 37 volunteers completed both treatment periods in 20 mg trial. All 40 participants completed both treatment periods in 40 mg trial. The 90 % CIs for the geometric mean ratios of the pharmacokinetic parameters (test:reference drug) were 0.93 ~ 1.04 for AUC_t and 0.97 ~ 1.08 for C_max in 20 mg trial. The 90 CIs were 0.94 ~ 1.02 for AUC_t and 1.00 ~ 1.11 for C_max in 40 mg trial. All parameters of two studies satisfy the range of bioequivalence criterion.

Conclusion

The obtained results indicated that pharmacokinetic exposure to Olmesartan 20 mg and 40 mg tablet was bioequivalent to that of Olmetec® 20 mg and 40 mg tablet, respectively.

Keywords: Olmesartan, Bioequivalence, Dose proportionality

Figures and Tables

Figure 1

Mean (SD) plasma concentration-time profiles of olmesartan medoxomil 20 mg after a single oral administration of two formulations in 37 healthy male subjects.

Figure 2

Mean (SD) plasma concentration-time profiles of olmesartan medoxomil 40 mg after a single oral administration of two formulations in 40 healthy male subjects.

Figure 3

Analysis of dose proportionality with Olmetec Tab® (A) AUCt/dose; (B) C_max/dose. 95% confidence intervals are shown in figures.

Figure 4

Analysis of dose proportionality with Olmesartan Tab (A) AUC_t/dose; (B) C_max/dose. 95% confidence intervals are shown in figures.

Table 1

Demographic characteristics of 20 mg trial and 40 mg trial subjects (mean ± SD [range])

^†unpaired t-test.

Table 2

Pharmacokinetic parameters of olmesartan medoxomil 20 mg and 40 mg after a single oral administration (20 mg trial and 40 mg trial) of two formulations (Reference: Olmetec Tab®, Test: Olmesartan Tab) in healthy male subjects (mean ± SD)

^†median[range]. ^*() : CV_intra % (intraindividual CV %). AUC_t: area under the plasma concentration-time curve to the last sampling time, C_max: maximum plasma concentration, T_max: time to C_max, t_1/2: terminal half-life.

Table 3

Bioequivalence assessment for the two formulations (20 mg trial and 40 mg trial)

Reference: Olmetec Tab®, Test: Olmesartan Tab.

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