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Analysis of institutional authors

Ochoa DAuthorRomán MAuthorZubiaur PAuthorBorobia AmAuthorAbad-Santos FCorresponding Author

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May 6, 2020
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Article

Effect of the most relevant CYP3A4 and CYP3A5 polymorphisms on the pharmacokinetic parameters of 10 CYP3A substrates

Publicated to:Biomedicines. 8 (4): E94- - 2020-04-01 8(4), DOI: 10.3390/biomedicines8040094

Authors: Saiz-Rodriguez, Miriam; Almenara, Susana; Navares-Gomez, Marcos; Ochoa, Dolores; Roman, Manuel; Zubiaur, Pablo; Koller, Dora; Santos, Maria; Mejia, Gina; Borobia, Alberto M; Rodriguez-Antona, Cristina; Abad-Santos, Francisco

Affiliations

Centro Nacional de Investigaciones Oncológicas - Author
Ctr Nacl Invest Oncol CNIO, Madrid 28029, Spain - Author
Fundacion Burgos por la Investigacion de la Salud - Author
Hosp Univ Burgos, Fdn Burgos Invest Salud, Reseach Unit, Burgos 09006, Spain - Author
Hosp Univ La Paz, Clin Pharmacol Dept, Madrid 28029, Spain - Author
Hospital Universitario de la Princesa - Author
Hospital Universitario La Paz - Author
UICEC Hosp Univ Princesa, Plataforma SCReN Spanish Clin Reseach Network, Inst Invest Sanitaria Princesa IP, Madrid 28006, Spain - Author
Univ Autonoma Madrid UAM, Inst Teofilo Hernando, Hosp Univ La Princesa, Clin Pharmacol Dept,Inst Invest Sanitaria La Prin, Madrid 28006, Spain - Author
Univ Autonoma Madrid, Sch Med, Pharmacol Dept, Madrid 28029, Spain - Author
Universidad Autónoma de Madrid - Author
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Abstract

© 2020 by the authors. Several cytochrome P450 (CYP) CYP3A polymorphisms were associated with reduced enzyme function. We aimed to evaluate the influence of these alleles on the pharmacokinetic parameters (PK) of several CYP3A substrates. We included 251 healthy volunteers who received a single dose of ambrisentan, atorvastatin, imatinib, aripiprazole, fentanyl, amlodipine, donepezil, olanzapine, fesoterodine, or quetiapine. The volunteers were genotyped for CYP3A4 and CYP3A5 polymorphisms by qPCR. To compare the PK across studies, measurements were corrected by the mean of each parameter for every drug and were logarithmically transformed. Neither CYP3A phenotype nor individual CYP3A4 or CYP3A5 polymorphisms were significantly associated with differences in PK. However, regarding the substrates that are exclusively metabolized by CYP3A, we observed a higher normalized AUC (p = 0.099) and a tendency of lower normalized Cl (p = 0.069) in CYP3A4 mutated allele carriers what was associated with diminished drug metabolism capacity. CYP3A4 polymorphisms did not show a pronounced influence on PK of the analysed drugs. If so, their impact could be detectable in a very small percentage of subjects. Although there are few subjects carrying CYP3A4 double mutations, the effect in those might be relevant, especially due to the majority of subjects lacking the CYP3A5 enzyme. In heterozygous subjects, the consequence might be less noticeable due to the high inducible potential of the CYP3A4 enzyme.

Keywords

cyp3a4cyp3a5Abcb1 polymorphismsCalcineurin inhibitorsCyp3a4Cyp3a5Cytochrome-p450 enzymesGenetic polymorphismsMetabolizing-enzymesPharmacokineticsRenal-transplant recipientsSingle nucleotide polymorphismTacrolimus dose requirementsTransporter polymorphismsTrough concentrations

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Biomedicines 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, 2020, it was in position 32/275, 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 World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 4.62. This 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: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 4.23 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 13.94 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-03, the following number of citations:

  • WoS: 69
  • Scopus: 77
  • Europe PMC: 29

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 2025-07-03:

  • 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: 146.
  • 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: 145 (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: 3.45.
  • 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/10486/693320

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 (Saiz-Rodríguez M) and Last Author (ABAD SANTOS, FRANCISCO).

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