Pharmacokinetic analysis and bioequivalence of Finasteride and Doxazosin formulated in a single tablet in comparison with the corresponding single agents

• Autor(a) principal: Guimaraes, Camila Leles
• Data de Publicação: 2023
• Outros Autores: Galvinas, Paulo Alexandre Rebelo, Baratta, Juliana Almeida, Pinto, Guilherme Araújo, Brandão, Amanda Hayashi, Sverdloff, Carlos, Rezende, Vinicius Marcondes
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Brazilian Journal of Health Review
• Texto Completo: https://ojs.brazilianjournals.com.br/ojs/index.php/BJHR/article/view/59429
• topic: Doxazosin; Finasteride; pharmacokinetics; benign prostatic hyperplasia; therapeutic equivalence; bioequivalence

The most commonly agents used to treat benign prostatic hyperplasia (BPH) in clinical practice are finasteride and doxazosin employed alone or in combination. Randomized clinical trials have shown that combination therapy with finasteride and doxazosin is superior to finasteride alone or placebo. However, decreased patient compliance may lead to unsatisfactorily therapeutic results. The aim of this study was to assess whether the combined pharmacokinetic profile for both finasteride and doxazosin was not significantly altered when these agents were co-administered, in comparison with their use as single agents. This was a randomized 6 sequences and 3 periods, crossover, comparative study of three medications: finasteride (5 mg), doxazosin (2 mg) (references), and the fixed combination containing 5 mg of finasteride and 2 mg of doxazosin in a single tablet (test). Plasma samples obtained from 30 eligible subjects were analyzed simultaneously for finasteride and doxazosin by HPLC coupled to a LC-MS/MS having cyproterone acetate and terazosin as internal standards. The statistical analysis showed no significant differences for AUC0-72h (finasteride: 245.3±87.8 vs. test: 240.5±93.1 and doxazosin: 183.0±42.9 vs. test: 188.8±45.6 ng.h.mL-1), AUC0-∞ (finasteride: 247.4±92.1 vs. test:  40.47±93.1 and doxazosin: 190.3±44.3 vs. test: 188.8±45.6 ng.h.mL-1), and Cmax (finasteride: 34.2±7.1 vs. test: 29.9±6.2 and doxazosin: 16.3±3.6 vs. test: 14.9±3.3 ng/mL). The mean ratios of AUC0-72h/AUC0-∞ for finasteride and doxazosin were 99.99% and 99.98%, respectively, indicating that the sampling time was adequate for both drugs. In summary, the current pharmacokinetic study demonstrated bioequivalence between the single agents and the corresponding agents in combination and provided further evidence for the lack of pharmacokinetic interaction between finasteride and doxazosin.