کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2085013 1545413 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cryopreserved human hepatocytes in suspension are a convenient high throughput tool for the prediction of metabolic clearance
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Cryopreserved human hepatocytes in suspension are a convenient high throughput tool for the prediction of metabolic clearance
چکیده انگلیسی

Hepatocyte assays, routinely used to assess the metabolic stability of new chemical entities, were recently improved by using hepatocytes in suspension instead of primary cultures [N. Blanchard, L. Richert, B. Notter, F. Delobel, P. David, P. Coassolo, T. Lavé, Impact of serum on clearance predictions obtained from suspensions and primary cultures of rat hepatocytes, Eur. J. Pharm. Sci. 23 (2004) 189–199].The aim of the present study was to investigate miniaturising the suspension assay by using cryopreserved human hepatocytes, i.e., 150,000 cells/well in 96-well plates, to predict hepatic clearance (CLH) in order to increase compound throughput and decrease cost and tissue requirements.For this, an evaluation was first carried out with rat hepatocytes. Then, human hepatocytes from various donors were used under these predetermined conditions, either immediately after isolation, either after a 20-h-cold storage period in UW or after cryopreservation.The values of CLint and CLH determined using human hepatocytes in suspension in 96-well plates, immediately after isolation, after cold storage or after cryopreservation, were comparable to those obtained with hepatocytes in primary culture. In particular, the use of cryopreserved human hepatocytes in suspension in a 96-well format appeared to be largely satisfactory as a tool for screening and ranking of compounds in the early phase of the drug discovery process.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 63, Issue 3, July 2006, Pages 347–355
نویسندگان
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