کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10299201 | 539696 | 2014 | 33 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacokinetic and pharmacodynamic interactions between almorexant, a dual orexin receptor antagonist, and desipramine
ترجمه فارسی عنوان
تعاملات فارماکوکینتیک و فارماکودینامیک بین آلومورسانت، آنتاگونیست گیرنده دوقلوی اکسین و دیزاپامین
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
روانپزشکی بیولوژیکی
چکیده انگلیسی
Almorexant is a dual orexin receptor antagonist (DORA) with sleep-enabling effects in humans. Insomnia is often associated with mental health problems, including depression. Hence, potential interactions with antidepressants deserve attention. Desipramine was selected as a model drug because it is mainly metabolized by CYP2D6, which is inhibited by almorexant in vitro. A single-center, randomized, placebo-controlled, two-way crossover study in 20 healthy male subjects was conducted to evaluate the pharmacokinetic and pharmacodynamic interactions between almorexant and desipramine. Almorexant 200Â mg or matching placebo (double-blind) was administered orally once daily in the morning for 10 days, and a single oral dose of 50Â mg desipramine (open-label) was administered on Day 5. Almorexant increased the exposure to desipramine 3.7-fold, suggesting that almorexant is a moderate inhibitor of desipramine metabolism through inhibition of CYP2D6. Conversely, desipramine showed no relevant effects on the pharmacokinetics of almorexant. Pharmacodynamic evaluations indicated that almorexant alone reduced visuomotor coordination, postural stability, and alertness, and slightly increased calmness. Desipramine induced a reduction in subjective alertness and an increase in pupil/iris ratio. Despite the increase in exposure to desipramine, almorexant and desipramine in combination showed the same pharmacodynamic profile as almorexant alone, except for prolonging reduced alertness and preventing the miotic effect of almorexant. Co-administration also prolonged the mydriatic effect of desipramine. Overall, repeated administration of almorexant alone or with single-dose desipramine was well tolerated. The lack of a relevant interaction with antidepressants, if confirmed for other DORAs, would be a key feature for a safer class of hypnotics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Neuropsychopharmacology - Volume 24, Issue 8, August 2014, Pages 1257-1268
Journal: European Neuropsychopharmacology - Volume 24, Issue 8, August 2014, Pages 1257-1268
نویسندگان
Hans G. Cruz, Justin L. Hay, Petra Hoever, Federica Alessi, Erik T. te Beek, Joop M.A. van Gerven, Jasper Dingemanse,