التفاصيل البيبلوغرافية
| العنوان: |
A Phase I Study Evaluating the Effect of Everolimus on the Pharmacokinetics of Midazolam in Healthy Subjects. |
| المؤلفون: |
Urva, Shweta1, Bouillaud, Emmanuel2, Delaney, Rosemary1, Jappe, Annette2, Cheung, Wing1 |
| 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] |
| قاعدة البيانات: |
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