Next Article in Journal
Microwave-Assisted Freeze-Drying of Monoclonal Antibodies: Product Quality Aspects and Storage Stability
Next Article in Special Issue
Extended Intake of Mulberry Leaf Extract Delayed Metformin Elimination via Inhibiting the Organic Cation Transporter 2
Previous Article in Journal
3D-Printed Solid Dispersion Drug Products
Previous Article in Special Issue
Paradoxical Effect of Grape Pomace Extract on Cisplatin-Induced Acute Kidney Injury in Rats
Open AccessArticle

In Vitro and In Vivo Assessment of Metabolic Drug Interaction Potential of Dutasteride with Ketoconazole

College of Pharmacy, Pusan National University, Busan 46241, Korea
Department of Pharmacy, College of Pharmacy, Mokpo National University, Jeonnam 58554, Korea
Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
Department of Physiology, College of Korean Medicine, Dongeui University, Busan 47227, Korea
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(12), 673;
Received: 3 November 2019 / Revised: 30 November 2019 / Accepted: 9 December 2019 / Published: 11 December 2019
(This article belongs to the Special Issue Pharmacokinetic Drug-Drug Interactions and Herb-Drug Interactions)
Dutasteride (DUT) is a selective, potent, competitive, and irreversible inhibitor of both type-1 and type-2 5α-reductase (5AR) commonly used in the treatment of benign prostatic hyperplasia and androgenetic alopecia. In the present study, we developed a simple and sensitive high-performance liquid chromatography with fluorescence detection (HPLC-FL) method for simultaneous determination of DUT and its major active metabolite, 6β-hydroxydutasteride (H-DUT). Next, the pharmacokinetic interactions of DUT with ketoconazole (KET), a potent CYP3A inhibitor, were comprehensively investigated. In vivo rat intravenous and oral studies revealed that the pharmacokinetics of DUT and H-DUT were significantly altered by the co-administration of KET. Furthermore, the in vitro microsomal metabolism, blood distribution, and protein-binding studies suggest that the altered pharmacokinetics of DUT could be attributed primarily to the inhibition of the DUT metabolism by KET. To the best of our knowledge, this is the first study to show the drug interaction potential of DUT with azole antifungal drugs including KET, together with a newly developed HPLC-FL method for the simultaneous quantification of DUT and H-DUT. View Full-Text
Keywords: dutasteride; 6β-hydroxy dutasteride; HPLC; fluorescence; ketoconazole; CYP3A dutasteride; 6β-hydroxy dutasteride; HPLC; fluorescence; ketoconazole; CYP3A
Show Figures

Figure 1

MDPI and ACS Style

Seo, S.-W.; Park, J.W.; Han, D.-G.; Kim, J.-M.; Kim, S.; Park, T.; Kang, K.-H.; Yang, M.H.; Yoon, I.-S. In Vitro and In Vivo Assessment of Metabolic Drug Interaction Potential of Dutasteride with Ketoconazole. Pharmaceutics 2019, 11, 673.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop