Transl Clin Pharmacol.  2016 Dec;24(4):175-182. 10.12793/tcp.2016.24.4.175.

Pharmacokinetics and safety profiles of tadalafil/tamsulosin HCl fixed-dose combination capsule under fasted and fed condition in healthy volunteers

• Jin BH
• Yoo BW
• Oh ES
• Yang S
• Jung J
• Park MS

• KMID: 2413839
• DOI: http://doi.org/10.12793/tcp.2016.24.4.175

Abstract

Co-administration of tadalafil and tamsulosin HCl in patients with benign prostate hyperplasia and erectile dysfunction is increasing in clinical settings. Development of fixed-dose combination (FDC) of tadalafil and tamsulosin HCl could contribute to improving patients' adherence and treatment efficacy. We evaluated the pharmacokinetics and safety profiles of a newly developed fixed-dose combination capsule of tadalafil 5 mg/tamsulosin HCl 0.4 mg in comparison with co-administration of each formulation in healthy volunteers under fasted and fed conditions. Two randomized, open-label, single-dose, two-way, crossover studies were completed in 29 subjects under fasted condition, and 33 subjects under fed condition. Serial blood sample collection for PK analysis was conducted up to 72 hours after dosing, and PK parameters were calculated using non-compartmental analysis. Geometric mean ratios and 90% confidence intervals of the C(max) and AUC(last) were used to evaluate comparative bioavailability. In both fasted and fed condition studies, the bioequivalence was established. The most common adverse drug reactions were orthostatic hypotension and headache with no statistical difference between treatment groups. All subjects with orthostatic hypotension recovered at follow-up test. Although changes in vital signs from baseline were statistically significant, there were no subjects with systolic blood pressure < 90 mmHg and there were no clinically meaningful signs or symptoms associated. FDC of tadalafil and tamsulosin HCl can be an alternative to co-administration of individual drugs for providing better compliance. Changes in blood pressure should be kept in mind when tadalafil and tamsulosin HCl are co-administered in clinical settings.

Keyword

pharmacokinetics; tadalafil; tamsulosin HCl; fixed-dose combination

MeSH Terms

Biological Availability
Blood Pressure
Compliance
Cross-Over Studies
Drug-Related Side Effects and Adverse Reactions
Erectile Dysfunction
Follow-Up Studies
Headache
Healthy Volunteers*
Humans
Hyperplasia
Hypotension, Orthostatic
Male
Pharmacokinetics*
Prostate
Tadalafil
Therapeutic Equivalency
Treatment Outcome
Vital Signs
Tadalafil

Figure

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  Figure 1. Plasma concentration-time profiles for (A) tadalafil, (B) tamsulosin HCl in fasted condition study as a fixed-dose combination or concomitant administration of individual drugs. Data are shown as mean ± SD. FDC, fixed-dose combination; Reference, concomitant administration of individual drugs.

• 

  Figure 2. Plasma concentration-time profiles for (A) tadalafil, (B) tamsulosin HCl in fed condition study as a fixed-dose combination or concomitant administration of individual drugs. Data are shown as mean ± SD. FDC, fixed-dose combination; Reference, concomitant administration of individual drugs.

• 

  Figure 3. Changes in (A) systolic blood pressure, (B) diastolic blood pressure over time in fasted condition study. Data are shown as mean ± SD. R, concomitantly administrated as individual drugs; T, administered as a fixed-dose combination

• 

  Figure 4. Changes in (A) systolic blood pressure, (B) diastolic blood pressure over time in fed condition study. Data are shown as mean ± SD. R, concomitantly administrated as individual drugs; T, administered as a fixed-dose combination

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