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

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

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 (Cmax) and area under the concentration-time curve from zero to last measurable time (AUClast) 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 Cmax and 1.014 (0.957–1.074) for AUClast, 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.

References

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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).
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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 %
Mean SD CV (%) Mean SD CV (%)
Tmax(h)+ 2.0 [1.5 – 6.0] 2.0 [1.0 – 4.0]
Cmax (ng/mL) 561.56 155.19 27.64 541.31 138.00 25.49 15.24 21.33
AUClast (ng·h/mL) 3560.70 938.58 26.36 3490.45 848.44 24.31 14.88 20.00
AUCinf (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]. AUClast, area under the plasma concentration time curve from 0 h to the last measurable time; AUCinf, area under the plasma concentration from 0 h to infinity; Cmax, maximum plasma concentration; tmax, time to reach Cmax; 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
Test Reference
Cmax (ng/mL) 540.368 526.147 1.027 0.969–1.088
AUClast (ng∙h/mL) 3440.653 3394.303 1.014 0.957–1.074
AUCinf (ng∙h/mL) 3558.072 3528.250 1.001 0.954–1.063

AUClast, area under the plasma concentration time curve from 0 h to the last measurable time; Cmax, maximum plasma concentration; AUCinf, area under the plasma concentration from 0 h to infinity; Cmax, maximum plasma concentration.

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