J Korean Soc Clin Pharmacol Ther.  2012 Dec;20(2):145-154.

Bioequivalence and Dose Proportionality of Olmesartan Medoxomil Formulations

• Cho SK
• Kim CO
• Yu SH
• Oh ES
• Jang SB
• Park YS
• Cho K
• Chung JY

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(R) 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 Cmax (maximum concentration) and AUCt (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 AUCt and 0.97 ~ 1.08 for Cmax in 20 mg trial. The 90 CIs were 0.94 ~ 1.02 for AUCt and 1.00 ~ 1.11 for Cmax 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(R) 20 mg and 40 mg tablet, respectively.

Keyword

Olmesartan; Bioequivalence; Dose proportionality

MeSH Terms

Chromatography, Liquid
Cross-Over Studies
Humans
Hypertension
Imidazoles
Male
Plasma
Receptors, Angiotensin
Tetrazoles
Therapeutic Equivalency
Imidazoles
Receptors, Angiotensin
Tetrazoles

Figure

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  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.

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  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.

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  Figure 3 Analysis of dose proportionality with Olmetec Tab® (A) AUCt/dose; (B) Cmax/dose. 95% confidence intervals are shown in figures.

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  Figure 4 Analysis of dose proportionality with Olmesartan Tab (A) AUCt/dose; (B) Cmax/dose. 95% confidence intervals are shown in figures.

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