Evaluation of the pharmacokinetics and food effects of a novel formulation tamsulosin 0.4 mg capsule compared with a 0.2 mg capsule in healthy male volunteers

Abstract

Tamsulosin, an alpha-1 adrenoreceptor antagonist, has been used as a primary option for medical treatment of benign prostate hyperplasia. An open-label, single-dose, randomized, three-treatment, three-period, three sequence crossover study was conducted to evaluate the pharmacokinetics (PKs) of 0.2 and 0.4 mg tamsulosin hydrochloride (HCl) in the fed versus the fasted state. Subjects were randomly assigned to three sequences and received one of the following treatments at each period: tamsulosin HCl 0.2 or 0.4 mg in the fed state with a high-fat meal, or tamsulosin HCl 0.4 mg in the fasted state. Blood samples for the PK analysis were collected at pre-dose and up to 48 h post-dose. The PK parameters were calculated by a non-compartmental method. The geometric mean ratio (GMR) and its 90% confidence intervals (CIs) of the plasma maximum concentration (Cmax) and area under concentration curve from time zero to last measurable concentration (AUClast) were calculated. Twenty-two subjects completed the study. The systemic exposure of tamsulosin 0.4 mg decreased approximately 9% in the fed state compared to the fasted state, and the time to reach peak concentration was slightly delayed in the fed state. The dose normalized GMR and its 90% CIs of Cmax and AUClast for 0.2 and 0.4 mg tamsulosin in the fed state were within 0.8 and 1.25 range. Systemic exposure of tamsulosin was decreased in the fed condition compared to the fasted condition. Linear PK profiles were observed between 0.2 and 0.4 mg tamsulosin in the fed state.

Trial registration: ClinicalTrials.gov Identifier: NCT02529800.

Keywords: Bioavailability; Pharmacokinetics; Tamsulosin.

Conflict of interest statement

Conflicts of Interest: - Authors: Jung J and Kim YI are employees of Hanmi Pharmaceutical Co., Ltd. The other authors report no conflicts of interest in this work. - Reviewers: Nothing to declare - Editors: Nothing to declare

Copyright © 2020 Translational and Clinical Pharmacology.

Figures

Figure 1. Study design.

0.2 mg, single administration of tamsulosin 0.2 mg; 0.4 mg, single administration of tamsulosin 0.4 mg.

Figure 2. Mean plasma concentration-time profiles of tamsulosin (A) in linear scale and (B) in semi-log scale after single oral administration of tamsulosin 0.2 mg (filled triangles) and tamsulosin 0.4 mg under fed conditions (filled circles) and tamsulosin 0.4 mg under fasting conditions (blank circles). Error bars denote the standard deviations.

Figure 3. Comparison of dose-normalized (A) Cmax and (B) AUClast between the tamsulosin 0.2 mg and tamsulosin 0.4 mg capsule under fed condition.

Cmax, maximum plasma concentration; AUClast, area under the curve from the time of administration to last measurable concentration.

Figure 4. Comparison of (A) Cmax and (B) AUClast of tamsulosin after oral administration of tamsulosin 0.4 mg with or without food.

Cmax, maximum plasma concentration; AUClast, area under the curve from the time of administration to last measurable concentration.