Pharmacokinetics and bioequivalence of two different 20 mg olmesartan tablets: A randomized, single-dose, two-period crossover study in healthy Korean male volunteers

Jieon Lee; AnHye Kim; Kyung-Sang Yu; Jae-Yong Chung; Sung-Vin Yim; Bo-Hyung Kim

doi:10.12793/tcp.2015.23.2.49

Journal List > Transl Clin Pharmacol > v.23(2) > 1082611

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Lee, Kim, Yu, Chung, Yim, and Kim: Pharmacokinetics and bioequivalence of two different 20 mg olmesartan tablets: A randomized, single-dose, two-period crossover study in healthy Korean male volunteers

Original Article

Translational and Clinical Pharmacology 2015;23(2):49-53.

Published online: 15 December 2015

DOI: https://doi.org/10.12793/tcp.2015.23.2.49

Pharmacokinetics and bioequivalence of two different 20 mg olmesartan tablets: A randomized, single-dose, two-period crossover study in healthy Korean male volunteers

Jieon Lee¹, AnHye Kim¹, Kyung-Sang Yu¹, Jae-Yong Chung², Sung-Vin Yim³, Bo-Hyung Kim^3,^∗

¹Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea

²Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam 13620, Korea

³Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul 02447, Korea

^∗Correspondence: B. H. Kim; Tel: +82-2-958-9326, Fax: +82-10-3736-4398, E-mail: bhkim98@khu.ac.kr

Received 3 May 201518 June 2015 Accepted 14 July 2015

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

Olmesartan is an angiotensin receptor blocker (ARB) and is widely used in clinical practice to treat hypertension. To compare the pharmacokinetic (PK) parameters and tolerability of two oral formulations of olmesartan (test drug: OMETAN® 20 mg tablet, reference drug: OLMETEC® 20 mg tablet) and assess their bioequivalence, a randomized, single dose, two-treatment crossover clinical study was conducted. At each period, 40 subjects received the test drug or the reference drug. Blood samples were collected at pre-dose and up to 48 h after study drug administration of each period. Plasma concentrations of olmesartan were measured using liquid chromatography-tandem mass spectrometry. To evaluate PK profiles, maximum plasma concentration (C_max) and area under the concentration-time curve from zero to last measurable time (AUC_last) were estimated using a non-compartmental method. Tolerability was evaluated based on the incidence of adverse events, vital signs, electrocardiograms, and laboratory tests. A total of 39 subjects completed the study. The geometric mean ratio and 90% confidence intervals (CI) of test drug to reference drug were 1.027 (0.969–1.088) for C_max and 1.014 (0.957–1.074) for AUC_last, respectively. There were no serious adverse events and both formulations of olmesartan were well tolerated. The OMETAN 20 mg tablet was judged to be bioequivalent to the OLMETEC 20 mg tablet.

Keywords: Olmesartan, Pharmacokinetics, Hypertension, Bioequivalence

References

1. von Bergmann K, Laeis P, Puchler K, Sudhop T, Schwocho LR, Gonzalez L. Olmesartan medoxomil: influence of age, renal and hepatic function on the pharmacokinetics of olmesartan medoxomil. J Hypertens Suppl. 2001; 19:S33–S40.

2. Nelson M. Drug treatment of elevated blood pressure. Aust Prescr. 2010; 33:108–112.

3. Jaques H. NICE guideline on hypertension. Eur Heart J. 2013; 34:406–408.

4. Greathouse M. A review of olmesartan medoxomil monotherapy: antihypertensive efficacy similar to that of other angiotensin II receptor blocker/hydrochlorothiazide combinations? Congest Heart Fail. 2002; 8:313–320.

5. Jiang J, Liu D, Hu P. Pharmacokinetic and safety profile of olmesartan medoxomil in healthy Chinese subjects after single and multiple administrations. Pharmazie. 2009; 64:323–326.

6. Rozza F, Trimarco V, Izzo R, Santoro M, Manzi MV, Marino M, et al. Antihypertensive response to combination of olmesartan and amlodipine does not depend on method and time of drug administration. High Blood Press Cardiovasc Prev. 2013; 20:25–32.

7. Domjan A, Kakuk P, Sandor J. The Helsinki Declaration at 50 years: comments on the 2013 modifications. Lege Artis Med. 2014; 24:152–158.

8. Jemal M. High-throughput quantitative bioanalysis by LC/MS/MS. Biomed Chromatogr. 2000; 14:422–429.

9. Julious SA. Sample sizes for clinical trials with normal data. Stat Med. 2004; 23:1921–1986.

10. Houin G. Bioequivalence studies: a new EMA guideline. Arzneimittelforschung. 2010; 60:169–170.

11. Yoshihara K, Gao Y, Shiga H, Wada DR, Hisaoka M. Population pharmacokinetics of olmesartan following oral administration of its prodrug, olmesartan medoxomil: in healthy volunteers and hypertensive patients. Clin Pharmacokinet. 2005; 44:1329–1342.

12. Johns EJ. The neural regulation of the kidney in hypertension and renal failure. Exp Physiol. 2014; 99:289–294.

13. Monhart V. Hypertension and chronic renal insufficiency-chronic kidney failure. Vnitr Lek. 2003; 49:388–394.

14. Volpe M, Tocci G. Olmesartan in the treatment of hypertension in elderly patients: a review of the primary evidence. Drugs Aging. 2013; 30:987–998.

Figure 1.

Mean plasma concentration versus time curves of olmesartan after oral administration of a single dose 20 mg olmesartan in healthy Korean subjects (n=39). The error bars represent the standard deviation of olmesartan plasma concentrations (Upper: linear scale, Lower: log scale).

Table 1.

Demographic characteristics of the study subjects

Characteristics	Mean	Median [min–max]	SD	CV (%)
Age (years)	24.9	25.0 [19.0–37.0]	3.5	14.0
Height (cm)	176.2	177.0 [166.0–186.0]	4.8	2.7
Weight (kg)	70.6	70.0 [56.2–95.0]	8.0	11.3

Table 2.

Pharmacokinetic parameters of olmesartan after a single administration of 20 mg test and reference drug in Korean healthy subjects (n = 39)

Parameters	Test drug (n = 39)			Reference drug (n = 39)			Intrasubject CV (%)	Intersubject CV %
Parameters	Mean	SD	CV (%)	Mean	SD	CV (%)	Intrasubject CV (%)	Intersubject CV %
T_max(h)⁺	2.0 [1.5 – 6.0]			2.0 [1.0 – 4.0]			–	–
C_max (ng/mL)	561.56	155.19	27.64	541.31	138.00	25.49	15.24	21.33
AUC_last (ng·h/mL)	3560.70	938.58	26.36	3490.45	848.44	24.31	14.88	20.00
AUC_inf (ng·h/mL)	3670.40	930.79	25.36	3628.67	882.33	24.32	14.19	20.40
CL/F (L/h)	5.80	1.45	25.09	5.83	1.41	24.20	–	–

⁺ Data are presented as median [min – max]. AUC_last, area under the plasma concentration time curve from 0 h to the last measurable time; AUC_inf, area under the plasma concentration from 0 h to infinity; C_max, maximum plasma concentration; t_max, time to reach C_max; CL/F, apparent clearance.

Table 3.

Pharmacokinetic parameters of olmesartan for the bioequivalence study with geometric mean ratios (test/reference) and 90% confidence intervals after a single dose of reference or test formulation in healthy Korean subjects

Parameters	Geometric mean		Test/Reference ratio	90% confidence interval
Parameters	Test	Reference	Test/Reference ratio	90% confidence interval
C_max (ng/mL)	540.368	526.147	1.027	0.969–1.088
AUC_last (ng∙h/mL)	3440.653	3394.303	1.014	0.957–1.074
AUC_inf (ng∙h/mL)	3558.072	3528.250	1.001	0.954–1.063

AUC_last, area under the plasma concentration time curve from 0 h to the last measurable time; C_max, maximum plasma concentration; AUC_inf, area under the plasma concentration from 0 h to infinity; C_max, maximum plasma concentration.

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