کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484368 | 1114308 | 2016 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Formation Rate-Limited Pharmacokinetics of Biologically Active Epoxy Transformers of Prodrug Treosulfan
ترجمه فارسی عنوان
فارماکوکینتیک محدود سازی فرمولاسیون ترانسفورماتورهای اپوکسی فعال بیولوژیک پروتئین ترئوسولفان
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کلمات کلیدی
TREOR.S.D.CLtotAUC0→∞HSCTLOQCmaxTreosulfan - treosulfanVSs - VSSrelative standard deviation - انحراف استاندارد نسبیBioanalysis - بیواناسیونvolume of distribution at steady state - حجم توزیع در حالت پایدارElimination - حذفrid - خلاص شدن از شرMetabolite kinetics - سینتیک متابولیتPharmacokinetics - فارماکوکینتیکnot applicable - قابل اجرا نیستlimit of quantitation - محدودیت مقدارDisposition - وضعProdrugs - پیش داروHematopoietic stem cell transplantation - پیوند مغز استخوانHPLC - کروماتوگرافی مایعی کاراtotal clearance - کل تایمر
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
چکیده انگلیسی
A prodrug treosulfan (TREO) is being evaluated in clinical trials as a myeloablative agent before hematopoietic stem cell transplantation. The active derivatives of TREO, monoepoxide (EBDM), and diepoxide (DEB) are formed in a pH-dependent nonenzymatic reaction. The aim of the study was to investigate pharmacokinetics of the TREO epoxy transformers in a rabbit model and explain the causes of low plasma concentrations of EBDM and DEB observed in patients receiving high-dose TREO before hematopoietic stem cell transplantation. New Zealand white rabbits (n = 5 per cohort) received an intravenous infusion of TREO (group I), injection of DEB (group II), and injection of a solution containing EBDM (group III). When EBDM and DEB were administered to the rabbits, they underwent a very rapid elimination (half-life 0.069 and 0.046 h) associated with a high systemic clearance (10.0 and 14.0 L hâ1 kgâ1). After administration of TREO, the t1/2 of EBDM was statistically equal to the t1/2 of the prodrug (1.6 h). To conclude, after administration of TREO, its epoxy transformers demonstrate a formation-limited elimination. Then EBDM and DEB have the same elimination half-life as TREO, but the levels of EBDM and DEB in the body, including plasma, are much lower than TREO on account of their inherently high clearance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 5, May 2016, Pages 1790-1797
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 5, May 2016, Pages 1790-1797
نویسندگان
MichaÅ RomaÅski, Anna Kasprzyk, Agnieszka Karbownik, Edyta SzaÅek, Franciszek K. GÅówka,