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Pharmacokinetic Study of a Soft Gelatin Capsule and a Solid-Supersaturatable SMEDDS Tablet of Dutasteride in Beagle Dogs

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background and Objective

Dutasteride, an analog of testosterone, a 5α-reductase inhibitor is widely used in the treatment of moderate to severe symptomatic benign prostatic hyperplasia. The aim of this study was to compare the pharmacokinetic characteristics of dutasteride in beagle dogs after oral administration of a conventional soft gelatin capsule (Avodart®) and a novel solid-supersaturatable soft-microemulsifying drug delivery system (SMEDDS) tablet.

Methods

In this comparative dissolution study, the dissolution of dutasteride was pH-independent for both formulations. Noncompartmental analysis and modeling approaches were carried out to determine the pharmacokinetic parameters of dutasteride.

Results

Approximately 90% of the drug dissolved in all media within 15 min, indicating that there was little difference in the dissolution rate of the solid-supersaturatable SMEDDS tablets and that of the commercial soft gelatin capsules. Using t test analysis, no statistically significant difference was detected in the pharmacokinetic parameters of the two formulations. The test/reference geometric mean ratios were 1.087 (90% confidence intervals 0.8529–1.3854) for the area under the plasma concentration versus time curve from 0 to the last time point (48 h) with a measurable concentration and 1.094 (90% confidence intervals 0.8909–1.3454) for maximum plasma concentration. Unfortunately, the bioequivalent criterium (0.8–1.25) was not met due to the small sample size, but the results of this study suggest a possible bioequivalence of dutasteride in the two formulations.

Conclusion

Based on the results of this study, the development of a tablet dosage form of dutasteride using a solid-supersaturatable SMEDDS should be considered for humans.

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Author information

Author notes

  1. Jeong-Soo Kim and Eun-Sol Ha contributed equally to this work as first author.

  2. Min-Soo Kim and In-hwan Baek contributed equally to this study.

Authors and Affiliations

  1. Dong-A ST Co. Ltd., Giheung-gu, Yongin, Gyeonggi, 446-905, Republic of Korea

    Jeong-Soo Kim

  2. College of Pharmacy, Pusan National University, 2, Busandaehak-ro 63 beon-gil, Geumjeong-gu, Busan, 46241, Republic of Korea

    Eun-Sol Ha, Heejun Park & Min-Soo Kim

  3. Department of Pharmaceutical Engineering, Inje University, Gyeongnam, 50834, Republic of Korea

    Du Hyung Choi

  4. College of Pharmacy, Kyungsung University, 309 Suyeong-ro, Nam-gu, Busan, 48434, Republic of Korea

    In-hwan Baek

Authors
  1. Jeong-Soo Kim
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  2. Eun-Sol Ha
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Corresponding authors

Correspondence to Min-Soo Kim or In-hwan Baek.

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Funding

This research was supported by Kyungsung University Research Grants in 2018.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics Approval

All animal procedures were approved by the Institutional Review Board of the KPC laboratory, a non-clinical contract research organization. The experiments were conducted in compliance with the Guidelines for the Care and Use of Laboratory Animals of the institute.

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Kim, JS., Ha, ES., Park, H. et al. Pharmacokinetic Study of a Soft Gelatin Capsule and a Solid-Supersaturatable SMEDDS Tablet of Dutasteride in Beagle Dogs. Eur J Drug Metab Pharmacokinet 45, 235–241 (2020). https://doi.org/10.1007/s13318-019-00594-4

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  • DOI: https://doi.org/10.1007/s13318-019-00594-4

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