A Drug‐Drug Interaction Study to Evaluate the Effect of TAS‐303 on CYP3A Activity in the Small Intestine and Liver
| العنوان: | A Drug‐Drug Interaction Study to Evaluate the Effect of TAS‐303 on CYP3A Activity in the Small Intestine and Liver |
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| المؤلفون: | Tomoe Fujita, Yoshinobu Sasaki, Masaki Kawai, Mika Maeda, Jinhong Huang, Yuji Kumagai, Makoto Nagaoka, Toru Takenaka |
| المصدر: | Journal of Clinical Pharmacology |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Male, PBPK, Simvastatin, animal structures, drug‐drug interactions, CYP3A, Hydrochloride, Midazolam, Administration, Oral, Pharmacology, 030226 pharmacology & pharmacy, clinical trials (CTRs), Models, Biological, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Pharmacokinetics, model & simulation, Oral administration, Intestine, Small, medicine, Cytochrome P-450 CYP3A, Humans, Pharmacology (medical), Drug Interactions, Computer Simulation, pharmaceutical R & D (PRD), biology, Adrenergic Uptake Inhibitors, Anticholesteremic Agents, Cytochrome P450, Small intestine, Healthy Volunteers, medicine.anatomical_structure, chemistry, Liver, 030220 oncology & carcinogenesis, Area Under Curve, biology.protein, Cytochrome P-450 CYP3A Inhibitors, Administration, Intravenous, clinical pharmacology, Anesthetics, Intravenous, medicine.drug |
| الوصف: | TAS‐303 (4‐piperidinyl 2,2‐diphenyl‐2‐[propoxy‐1,1,2,2,3,3,3‐d7] acetate hydrochloride) is a novel selective noradrenaline reuptake inhibitor being developed for the treatment of stress urinary incontinence. An in vitro study and a physiologically based pharmacokinetic model simulation showed that TAS‐303 had inhibitory potential against cytochrome P450 (CYP) 3A. This open‐label, single‐group study investigated the effect of TAS‐303 on CYP3A activity by evaluating the pharmacokinetics (PK) of single‐dose oral simvastatin 5 mg or intravenous midazolam 1 mg after repeated oral administration of TAS‐303 3 mg in 12 healthy participants. TAS‐303 plus simvastatin resulted in a 1.326‐fold and a 1.420‐fold increase of simvastatin in peak plasma concentration and area under the plasma concentration‐time curve from time zero to time t, where t is the final time of detection (AUC0‐t), respectively. The addition of midazolam resulted in a 1.090‐fold increase in the midazolam AUC0‐t. TAS‐303 had a weak PK interaction with simvastatin but no apparent interaction with midazolam. TAS‐303 at 3 mg/day is a weak inhibitor of intestinal but not hepatic CYP3A activity. No clinically important safety concerns related to TAS‐303 were raised. |
| اللغة: | English |
| تدمد: | 1552-4604 0091-2700 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::962caa7db3e0fe22bacd03427bb0e1ee http://europepmc.org/articles/PMC7318569 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....962caa7db3e0fe22bacd03427bb0e1ee |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15524604 00912700 |
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