کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9012295 | 1124553 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
New model for intravenous drug administration and blood sampling in the awake rat, designed to increase quality and throughput for in vivo pharmacokinetic analysis
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
CmaxADMEHCTNCEtmaxtotal plasma clearanceAUC - AUCLC-MS/MS - LC-MS / MSt1/2 - t1 / 2Absorption distribution metabolism excretion - جذب توزیع متابولیسم توزیعVolume of distribution - حجم توزیعmaximum plasma concentration - حداکثر غلظت پلاسماtime to reach Cmax - زمان برای رسیدن به Cmaxpharmacokinetic - فارماکوکینتیکIn vivo model - مدل in vivoarea under the curve - منطقه تحت منحنیnew chemical entity - موجودی شیمیایی جدیدRat - موش صحراییPlasma half-life - نیمه عمر پلاسماHaematology - هماتولوژیhaematocrit - هماتوکریتliquid chromatography coupled to tandem mass spectrometry - کروماتوگرافی مایع همراه با طیف سنجی جرمی دو طرفه
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Introduction: There is a continuing need for increased throughput in the examination of new chemical entities (NCEs) in terms of the pharmacokinetic (PK) parameters. The aim was to validate a new study method designed to improve throughput and reduce inter-animal variability and animal number requirement in routine bioavailability and plasma PK studies of NCEs in awake rats. Methods: The design uses a new method for intravenous (iv) administration via the saphenous vein in combination with serial blood sampling via the tail vein. The multiple sampling method was compared with single sampling (decapitation) and the effect on haematocrit (Hct) levels was studied. Direct injection in the saphenous vein was compared to iv administration using an indwelling jugular catheter. Results: Using structurally different NCEs, it was shown that a combination of direct injection via the saphenous vein and multiple sampling from the tail vein produces comparable plasma concentrations and subsequent PK results to the comparator methods. Furthermore, Hct levels remained within recommended levels using a total blood sampling volume of up to 2.1 ml/day for rats with a body weight of around 250 g. Discussion: The new model increases throughput by avoiding the time required for preparative surgery, increases quality by allowing inter-animal comparison of major PK parameters as concentration time curves can be obtained from each animal, and reduces the number of animals required.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmacological and Toxicological Methods - Volume 52, Issue 2, SeptemberâOctober 2005, Pages 293-301
Journal: Journal of Pharmacological and Toxicological Methods - Volume 52, Issue 2, SeptemberâOctober 2005, Pages 293-301
نویسندگان
Claire Mackie, Koen Wuyts, Marc Haseldonckx, Saskia Blokland, Petra Gysemberg, Iris Verhoeven, Philip Timmerman, Marjoleen Nijsen,