التفاصيل البيبلوغرافية
| العنوان: |
A Phase I Study Evaluating the Effect of Everolimus on the Pharmacokinetics of Midazolam in Healthy Subjects. |
| المؤلفون: |
Urva, Shweta, Bouillaud, Emmanuel, Delaney, Rosemary, Jappe, Annette, Cheung, Wing |
| المصدر: |
Journal of Clinical Pharmacology; Apr2013, Vol. 53 Issue 4, p444-450, 7p |
| مصطلحات موضوعية: |
BLOOD testing, COMBINATION drug therapy, CONFIDENCE intervals, ELECTROCARDIOGRAPHY, GENE expression, MIDAZOLAM, RESEARCH funding, DATA analysis software, DESCRIPTIVE statistics, EVEROLIMUS |
| مستخلص: |
The selective mammalian target of rapamycin (mTOR) inhibitor everolimus has demonstrated competitive inhibition of cytochrome P450 enzyme (CYP) 3A4 in vitro; however, its influence on CYP3A4 activity in humans is unknown. This study examined the influence of everolimus on the pharmacokinetics of midazolam, a sensitive CYP3A4/5 substrate, and its 1-hydroxy metabolite in 25 healthy male subjects. Compared with administration of oral midazolam 4 mg/day alone, coadministration with everolimus 10 mg/day increased the midazolam maximum plasma concentration (Cmax) by 25% and the area under the plasma concentration-time curve (AUC) by 30%. The Cmax and AUC of 1-hydroxymidazolam increased by 20% and 25%, respectively. Concomitant administration of everolimus with midazolam did not change the midazolam metabolic ratio (i.e., the ratio of 1-hydroxymidazolam AUC to midazolam AUC) or the midazolam or 1-hydroxymidazolam terminal half-lives (geometric mean ratios for midazolam + everolimus vs. midazolam alone of 0.96, 1.03, and 1.06, respectively). These results suggest everolimus may affect the bioavailability, but not the systemic clearance, of orally coadministered CYP3A4 substrate drugs. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Clinical Pharmacology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
