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首页> 外文期刊>Journal of pharmaceutical sciences. >Diphenhydramine active uptake at the blood-brain barrier and its interaction with oxycodone in vitro and in vivo.
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Diphenhydramine active uptake at the blood-brain barrier and its interaction with oxycodone in vitro and in vivo.

机译：苯海拉明在血脑屏障中的活性摄取及其在体外和体内与羟考酮的相互作用。

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摘要

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 K(i) value of 106 muM. DPHM also competitively inhibited oxycodone uptake with a K(i) value of 34.7 muM. 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 K(i) values.
机译：苯海拉明（DPHM）和羟考酮是弱碱，能够形成阳离子。两种药物均在血脑屏障（BBB）上具有主动摄取。因此，通过竞争相同的摄取转运系统，它们之间可能发生药代动力学相互作用。本研究的实验旨在研究DPHM在BBB中的转运及其在体外和体内与羟考酮的相互作用。在体外，使用条件永生化的大鼠脑毛细管内皮细胞（TR-BBB13细胞）研究了药物之间的相互作用。使用脑和血液微透析在大鼠中研究了体外发现的体内相关性。 DPHM在体外积极转运穿过BBB（TR-BBB13细胞）。羟考酮竞争性抑制DPHM摄取，K（i）值为106μM。 DPHM还竞争性抑制羟考酮的摄取，K（i）值为34.7μM。在大鼠中，DPHM在脑组织间质液（ISF）中的未结合浓度比在血液中高五倍，从而证明了净的主动摄取。在体内DPHM和羟考酮之间没有显着的相互作用。这与体外实验的结果相符，因为在体内不会引起不良影响的未结合血浆浓度远低于K（i）值。

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