کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2485496 1114356 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Diphenhydramine Active Uptake at the Blood–Brain Barrier and Its Interaction with Oxycodone in vitro and in Vivo
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Diphenhydramine Active Uptake at the Blood–Brain Barrier and Its Interaction with Oxycodone in vitro and in Vivo
چکیده انگلیسی

Diphenhydramine (DPHM) and oxycodone are weak bases that are able to form cations. Both drugs show active uptake at the blood–brain barrier (BBB). There is thus a possibility for a pharmacokinetic interaction between them by competition for the same uptake transport system. The experiments of the present study were designed to study the transport of DPHM across the BBB and its interaction with oxycodone in vitro and in vivo. In vitro, the interaction between the drugs was studied using conditionally immortalized rat brain capillary endothelial cells (TR-BBB13 cells). The in vivo relevance of the in vitro findings was studied in rats using brain and blood microdialysis. DPHM was actively transported across the BBB in vitro (TR-BBB13 cells). Oxycodone competitively inhibited DPHM uptake with a Ki value of 106 μM. DPHM also competitively inhibited oxycodone uptake with a Ki value of 34.7 μM. In rats, DPHM showed fivefold higher unbound concentration in brain interstitial fluid (ISF) than in blood, confirming a net active uptake. There was no significant interaction between DPHM and oxycodone in vivo. This accords with the results of the in vitro experiments because the unbound plasma concentrations that could be attained in vivo, without causing adverse effects, were far below the Ki values. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3912–3923, 2011

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 9, September 2011, Pages 3912–3923
نویسندگان
, , , , , , , , , ,