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Abstract
Tamsulosin is an effective therapeutic option for lower urinary tract symptoms, as it selectively blocks α1A- and α1D-adrenoceptors in the bladder and prostate. The purpose of this study was to evaluate the bioequivalence in the pharmacokinetics (PK) of two 0.2 mg tamsulosin formulations when administered as the reference formulation (Yuropa® sustained-release tablet) vs. the test formulation (Yutanal® capsule) in healthy male subjects. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 37 healthy volunteers. The 0.2 mg of tamsulosin as the test or the reference formulation were administered during each period, and serial blood samples were collected up to 36 hours after dosing for PK analyses. A non-compartmental analysis was used to estimate the PK parameters. Geometric mean ratios (GMR) and 90% confidence intervals (CIs) were calculated for the two formulations to compare the maximum concentration (Cmax) and the area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast). The mean Cmax and AUClast for the test formulation were 6.19 μg/L and 71.30 μg.h/L, respectively, and 5.76 μg/L and 70.38 μg.h /L for the reference formulation, respectively. The GMRs (90% CIs) of the Cmax and AUClast between the two formulations were 1.09 (1.01–1.17) and 1.03 (0.96–1.10), respectively. Tamsulosin 0.2 mg as the test formulation exhibited bioequiva-lent PK profiles to those of the reference formulation. Therefore, the test formulation is expected to be an alternative to the reference formulation without concerns about differences in drug exposure.
References
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Figure 1.
Mean ± SD plasma concentration-time profiles of tamsulosin after single doses of the test (black circles) and the reference formulations (white circles) of tamsulosin hydrochloride 0.2 mg in healthy subjects (A: linear scale B: log scale).
Figure 2.
Individual (A) AUClast and (B) Cmax of tamsulosin after single doses of the test and the reference formulations of tamsulosin hydrochloride 0.2 mg in healthy subjects.
Table 1.
Pharmacokinetic parameters of tamsulosin in 37 subjects after they received a single dose of tamsulosin hydrochloride 0.2 mg of the test and the reference formulations
| Test formulation | Reference formulation | Geometric mean ratio (90% confidence interval) | |
|---|---|---|---|
| Tmax(h)a | 5.0 [2.0–7.0] | 5.0 [3.0–6.0] | |
| Cmax (μg/L) | 6.19±2.04 | 5.76±2.21 | 1.09 (1.01–1.17) |
| AUClast (μg·h/L) | 71.30±27.55 | 70.38±30.52 | 1.03 (0.96–1.10) |
| AUCinf (μg·h/L) | 78.04±30.89 | 77.66±37.58 | |
| t1/2 (h) | 8.67±2.03 | 8.85±2.98 | |
| CL/F (L/h) | 3.01±1.28 | 3.23±1.63 | |
| Vd/F (L) | 36.30±15.38 | 36.85±12.52 |
a Median [range]. Tmax, time to reach the maximum blood concentration after administration of drug; Cmax, maximum plasma concentration of drug; AUClast, area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration; AUCinf, area under the plasma concentration-time curve from time 0 to infinity; t1/2, terminal elimination half-life; CL/F, apparent clearance; Vd/ F, apparent volume of distribution.
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