کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2566366 | 1128081 | 2007 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
P-glycoprotein and cytochrome P450 3A4 involvement in risperidone transport using an in vitro Caco-2/TC7 model and an in vivo model
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کلمات کلیدی
P-gpCLRtmaxMRPCYP3A4POVMRTCyPOATPMDRCmaxbasolateral to apicalP-glycoprotein - P-گلیکوپروتئینPer os - per osmaximum plasma concentration - حداکثر غلظت پلاسماEfflux transport - حمل و نقل تخلیهIntravenous - داخل وریدیRisperidone - ریسپریدون Mean retention time - زمان متوسط نگهداریCaco-2 cells - سلول های Caco-2Cytochrome P450 - سیتوکروم پی۴۵۰Fraction absorbed - فراکسیون جذب می شودMultidrug resistance - مقاومت چند داروییarea under the curve - منطقه تحت منحنیefflux ratio - نسبت خروجیApparent permeability - نفوذ پذیری ظاهریPapp - پاپmultidrug resistance associated protein - پروتئین مرتبط با مقاومت چند داروییOrganic anion transporting polypeptides - پلیپپتید های حمل آنیون های آلیPept1 - پپت 1high performance liquid chromatography - کروماتوگرافی مایع با کارایی بالاHPLC - کروماتوگرافی مایعی کاراrenal clearance - کلیهkapp - گنجه
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The possible involvement of P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 in risperidone transport was investigated using in vitro and in vivo models. Firstly, uptake studies were performed on a Caco-2/TC7 cell monolayer; the effects of 1 μg mlâ 1 risperidone on apparent permeability were determined for secretory and absorptive directions, in the presence or absence of various P-gp and CYP3A4 inhibitors (verapamil, ketoconazole, erythromycin), and of an associated multidrug-resistant protein inhibitor (indomethacin). Secondly, on a conscious rat model, risperidone pharmacokinetic parameters, notably absorption parameters, were determined using compartmental and deconvolution methods. Three groups of seven rats received respectively an IV risperidone dose, an oral risperidone dose (PO group) and the same oral risperidone dose after verapamil administration (POV group). No formation of 9-hydroxyrisperidone was observed on Caco-2 cells after risperidone administration; there was no evidence that intestinal CYP3A4 is involved in risperidone metabolising. Risperidone secretory permeation was higher than absorptive permeation. Verapamil increased risperidone absorption permeation and decreased its secretory permeation. Indomethacin did not modify these permeation values. In rats, verapamil led to an increase in both risperidone and 9-hydroxyrisperidone plasmatic concentrations. The fraction absorbed in the verapamil group was 3.18 times higher than in the oral group (65.9% and 20.7% for POV group and PO group). The absorption rate constant was lower in the verapamil group. Our results indicate that P-gp decreases the intestinal absorption of risperidone and that intestinal CYP3A4 is not involved in risperidone metabolism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Progress in Neuro-Psychopharmacology and Biological Psychiatry - Volume 31, Issue 4, 9 May 2007, Pages 878-886
Journal: Progress in Neuro-Psychopharmacology and Biological Psychiatry - Volume 31, Issue 4, 9 May 2007, Pages 878-886
نویسندگان
Etienne Cousein, Christine Barthélémy, Stéphanie Poullain, Nicolas Simon, Sophie Lestavel, Virginie Williame, Etienne Joiris, Cécile Danel, Véronique Clavey, Denis Brossard, Hugues Robert, Sylvie Crauste-Manciet, Claude Vaccher, Pascal Odou,