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Abstract
Background:
To evaluate the pharmacokinetic properties of daily oral doses of tamsulosin administered to fasted healthy Korean male volunteers for 5 days.
Methods:
In a randomized, open-label, multiple-dose, two-period, crossover study, all 44 subjects were randomly assigned in a 1:1 ratio to receive a newly developed generic capsule formulation (test) or a branded capsule formulation (reference) of tamsulosin 0.2 mg, followed by a 10-day washout period and administration of the other formulation. Plasma concentrations of tamsulosin were assessed after administration of five-day multiple doses, using HPLC-MS/MS. Clinical and laboratory adverse events (AE) were assessed.
Results:
The mean (SD) pharmacokinetic properties with the test and reference formulations were as follows: Css, max, 9.0 (2.9) and 8.4 (2.6) ng/mL, respectively; median (range) tmax, 4 (2-6) and 5 (2-7) hours; AUCτ, 93.7 (31.5) and 88.2 (29.3) ng × h/mL; and t$$ 9.5 (2.6) and 10.0 (2.7) hours. The volume of distribution and clearance after oral administration of tamsulosin were 0.5 L/kg, and 0.04 L/h/kg, respectively. The accumulation ratios for 0.2 mg once-daily dosing regimen were 1.2. The 90% CIs of the geometric mean ratios for the log-transformed AUCτ (1.005-1.131) and Css, max (1.000-1.136) values were within the acceptable range for bioequivalence. No serious AE was reported during the study. Both formulations were well tolerated.
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Figure 2.
Mean (SD) plasma tamsulosin concentration-time profiles after administration of multiple 0.2-mg/day doses of two formulations of tamsulosin in 41 healthy Korean male volunteers.
Table 1.
Mean (SD) tamsulosin pharmacokinetic parameters following multiple doses of two tamsulosin formulations in healthy Korean male subjects (n = 41)
AUCτ, area under the plasma concentration-time curve over the dosing interval after multiple-dose administration, AUC∞, area under the plasma concentration-time curve to infinity; Css,max, steady-state maximum plasma concentration, Css,min, steady-state minimum plasma concentration, Css,av, steady-state average plasma concentration, FI, fluctuation index, tmax, time to reach maximum plasma concentration, t1/2, half-life, R, accumulation ratio, CI/F, apparent oral clearance, Vd/F, apparent volume of distribution. †median (range). *P < 0.05 between the two groups by paired t-test. **P < 0.05 between the two groups by Wilcoxon signed rank test.
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