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. 2023 Oct 31;13(11):1566.
doi: 10.3390/jpm13111566.

Food Administration and Not Genetic Variants Causes Pharmacokinetic Variability of Tadalafil and Finasteride

Gonzalo Villapalos-García  1 , Pablo Zubiaur  1 , Cristina Marián-Revilla  1 , Paula Soria-Chacartegui  1 , Marcos Navares-Gómez  1 , Gina Mejía-Abril  1 , Andrea Rodríguez-Lopez  1 , Eva González-Iglesias  1 , Samuel Martín-Vílchez  1 , Manuel Román  1 , Dolores Ochoa  1 , Francisco Abad-Santos  1   2
Affiliations

Food Administration and Not Genetic Variants Causes Pharmacokinetic Variability of Tadalafil and Finasteride

Gonzalo Villapalos-García et al. J Pers Med. .

Abstract

Tadalafil and finasteride are used in combination for the management of benign prostatic hyperplasia (BPH). Genetic variations in genes involved in the metabolism and transport of tadalafil or finasteride (i.e., pharmacogenes) could affect their pharmacokinetic processes altering their drug exposure, efficacy, and toxicity. The main objective of this study was to investigate the effects of variants in pharmacogenes on the pharmacokinetics of tadalafil and finasteride. An exploratory candidate gene study involving 120 variants in 33 genes was performed with 66 male healthy volunteers from two bioequivalence clinical trials after administration of tadalafil/finasteride 5 mg/5 mg under fed or fasting conditions. Afterwards, a confirmatory study was conducted with 189 male and female volunteers receiving tadalafil 20 mg formulations in seven additional bioequivalence clinical trials. Regarding tadalafil, fed volunteers showed higher area in the time-concentration curve (AUC∞), maximum plasma concentration (Cmax), and time to reach Cmax (tmax) compared to fasting volunteers; male volunteers also showed higher AUC∞ and Cmax compared to female volunteers. Furthermore, fed volunteers presented higher finasteride AUC∞, Cmax and tmax compared to fasting individuals. Variants in ABCC3, CYP1A2, CES1, NUDT15, SLC22A1/A2 and UGT2B10 were nominally associated with pharmacokinetic variation in tadalafil and/or finasteride but did not remain significant after correction for multiple comparisons. Genetic variation did not demonstrate to clinically impact on the pharmacokinetics of finasteride and tadalafil; however, additional studies with larger sample sizes are needed to assess the effect of rare variants, such as CYP3A4*20 or *22, on tadalafil and finasteride pharmacokinetics.

Keywords: finasteride; food administration; pharmacogenetics; tadalafil.

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Conflict of interest statement

Francisco Abad-Santos and Dolores Ochoa have been consultants or investigators in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Cinfa, FAES, Farmalider, Ferrer, GlaxoSmithKline, Galenicum, Gilead, Italfarmaco, Janssen-Cilag, Kern, Moderna, MSD, Normon, Novartis, Servier, Silverpharma, Teva, and Zambon. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Tadalafil AUC∞/DW in clinical trials 3, 4, 5, 6, 7, 8, and 9 according to feeding conditions. * p < 0.05 after univariate and multivariate analysis.
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