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Effects of itraconazole and rifampicin on the pharmacokinetics and safety of youkenafil in healthy Chinese male subjects
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  • Keli Wang,
  • Juefang Ding,
  • Xianjing Li,
  • Wenjing Guo,
  • Xingyu Zhu,
  • Yue Su,
  • Luning Sun,
  • Huan Zhou,
  • Li Ding
Keli Wang
China Pharmaceutical University - Jiangning Campus
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Juefang Ding
Nanjing Jiening Pharmaceutical Technology Co., LTD
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Xianjing Li
China Pharmaceutical University - Jiangning Campus
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Wenjing Guo
China Pharmaceutical University - Jiangning Campus
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Xingyu Zhu
The First Affiliated Hospital of Bengbu Medical College
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Yue Su
The First Affiliated Hospital of Bengbu Medical College
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Luning Sun
The First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital
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Huan Zhou
First Affiliated Hospital of Bengbu Medical College
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Li Ding
China Pharmaceutical University - Jiangning Campus

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Abstract

Aims: Youkenafil is a novel selective phosphodiesterase type 5 inhibitor to treat erectile dysfunction. Since it was mainly metabolized through cytochrome P450 3A4/5 (CYP3A4/5) in vitro, the effects of itraconazole and rifampicin (potent CYP3A4/5 inhibitor and inducer, respectively) on the pharmacokinetics of youkenafil and its main metabolite (M1) were investigated in two clinical studies. Methods: Each study enrolled thirty healthy male subjects. In study 1, subjects were given a single dose of youkenafil (50 mg on Days 1 and 13) and multiple doses of itraconazole (200 mg once daily from Days 6 to 14). In study 2, subjects were given a single dose of youkenafil (100 mg on Days 1 and 20) and multiple doses of rifampicin (600 mg once daily from Days 6 to 20). Results: Itraconazole significantly increased the systemic exposure to youkenafil and M1. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) for the AUC0-t, AUC0-∞ and Cmax of youkenafil were 1198.58% (900.33%–1595.63%), 1162.54% (874.69%–1545.11%) and 632.17% (500.40%–798.64%), respectively. Conversely, rifampicin significantly decreased the systemic exposure to youkenafil but had a slight effect on M1. The GMRs (90% CI) for the AUC0-t, AUC0-∞ and Cmax of youkenafil were 1.72% (1.27%–2.33%), 1.80% (1.33%–2.43%) and 1.77% (1.27%–2.47%), respectively. All subjects tolerated well in both studies. Conclusion: Itraconazole increased youkenafil AUC and Cmax by 12- and 6-fold, respectively. Rifampicin decreased youkenafil AUC and Cmax both by about 98%. Therefore, combined administration of youkenafil with potent inhibitors or inducers of CYP3A4/5 should be avoided or carefully monitored.