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Analysis of institutional authors

Zubiaur PAuthorOchoa DAuthorAbad-Santos FCorresponding Author

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November 1, 2021
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Effects of Cytochrome P450 and Transporter Polymorphisms on the Bioavailability and Safety of Dutasteride and Tamsulosin

Publicated to:Frontiers in Pharmacology. 12 718281- - 2021-10-07 12(), DOI: 10.3389/fphar.2021.718281

Authors: Villapalos-García G; Zubiaur P; Navares-Gómez M; Saiz-Rodríguez M; Mejía-Abril G; Martín-Vílchez S; Román M; Ochoa D; Abad-Santos F

Affiliations

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas , Hospital Universitario de la Princesa - Author
Complejo Asistencial Universitario de Burgos - Author
Hosp Univ Burgos HUBU, Res Unit, Burgos, Spain - Author
Hosp Univ La Princesa, Inst Invest Sanitaria La Princesa IP, Platform SCReN Spanish Clin Res Network, Unidad Invest Clin & Ensayos Clin UICEC, Madrid, Spain - Author
Hospital Universitario de la Princesa - Author
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Diges, Madrid, Spain - Author
Univ Autonoma Madrid, Hosp Univ La Princesa, Sch Med, Inst Teofilo Hernando,Clin Pharmacol Dept,Inst In, Madrid, Spain - Author
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Abstract

Dutasteride and tamsulosin are one of the first-line combination therapies for the management of benign prostatic hyperplasia (BPH). Despite being more effective than monotherapies, they produce frequent adverse drug reactions (ADRs). Institutions such as Food and Drug Administration and European Medicines Agency recommend precaution with CYP2D6 poor metabolizers (PMs) that receive CYP3A4 inhibitors and tamsulosin. However, no specific pharmacogenetic guideline exists for tamsulosin. Furthermore, to date, no pharmacogenetic information is available for dutasteride. Henceforth, we studied the pharmacokinetics and safety of dutasteride/tamsulosin 0.5 mg/0.4 mg capsules according to 76 polymorphisms in 17 candidate pharmacogenes. The study population comprised 79 healthy male volunteers enrolled in three bioequivalence, phase-I, crossover, open, randomized clinical trials with different study designs: the first was single dose in fed state, the second was a single dose in fasting state, and the third was a multiple dose. As key findings, CYP2D6 PMs (i.e., *4/*4 and *4/*5 subjects) and intermediate metabolizers (IMs) (i.e., *1/*4, *1/*5, *4/*15 individuals) presented higher AUC (p = 0.004), higher t1/2 (p = 0.008), and lower Cl/F (p = 0.006) when compared with NMs (*1/*1 individuals) and UMs (1/*1 × 2 individuals) after multiple testing correction. Moreover, fed volunteers showed significantly higher tmax than fasting individuals. Nominally significant associations were observed between dutasteride exposure and CYP3A4 and CYP3A5 genotype and between tamsulosin and ABCG2, CYP3A5, and SLC22A1 genotypes. No association between the occurrence of adverse drug reactions and genotype was observed. Nonetheless, higher incidence of adverse events was found in a multiple-dose clinical trial. Based on our results, we suggest that dose adjustments for PMs and UMs could be considered to ensure drug safety and effectiveness, respectively. Further studies are warranted to confirm other pharmacogenetic associations.

Keywords

cyp2d6cyp3a4dutasteridegenotypepharmacogeneticspharmacokineticstamsulosinConsortium cpic guidelinesCyp2d6Cyp3a4DutasteridePharmacogeneticsPharmacokineticsTamsulosin

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Frontiers in Pharmacology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 50/279, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.82, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-18, the following number of citations:

  • WoS: 3
  • Scopus: 6

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-18:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 18.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 25 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 2.5.
  • The number of mentions on the social network X (formerly Twitter): 5 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/716820

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Villapalos-García G) and Last Author (ABAD SANTOS, FRANCISCO).

the author responsible for correspondence tasks has been ABAD SANTOS, FRANCISCO.