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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >P-glycoprotein interactions of nefazodone and trazodone in cell culture.
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P-glycoprotein interactions of nefazodone and trazodone in cell culture.

机译：奈法唑酮和曲唑酮在细胞培养中的P-糖蛋白相互作用。

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摘要

This study investigated the effects of nefazodone (NFZ) and trazodone (TZD) on P-glycoprotein (P-gp) activity and expression in cell culture. NFZ and TZD showed no differential transport between the basolateral to apical and apical to basolateral direction across Caco-2 cell monolayers. Transport in either direction was not affected by verapamil. NFZ was a potent inhibitor (IC50 = 4.7 microM) of rhodamine123 (Rh123) B to A transport across Caco-2 cell monolayers, while TZD had minimal effect. Following 72-hour exposure of LS180V cells to NFZ and TZD (10 microM), a twofold increase in immunoreactive P-gp was observed. Rh123 accumulation into these cells was reduced to 65% and 74% of control by NFZ and TZD (10 microM), respectively. It was concluded that differential rates of transport of NFZ and TZD in Caco-2 cells were not evident. However, NFZ is an inhibitor of P-gp activity at clinically relevant in vivo concentrations and may have the potential to increase bioavailability of coadministered compounds that are substrates for transport. Concentrations of NFZ and TZD achieved in the intestine after chronic oral dosing may induce P-gp expression and reduce absorption of coadministered drugs.
机译：这项研究调查了奈法唑酮（NFZ）和曲唑酮（TZD）对P-糖蛋白（P-gp）活性和细胞培养物中表达的影响。 NFZ和TZD在跨Caco-2细胞单层的基底外侧到顶端方向与顶端到顶端外侧之间没有差异传输。维拉帕米不影响任一方向的运输。 NFZ是若丹明123（Rh123）B对A跨Caco-2细胞单层转运的有效抑制剂（IC50 = 4.7 microM），而TZD的影响最小。将LS180V细胞暴露于NFZ和TZD（10 microM）72小时后，观察到免疫反应性P-gp增加了两倍。通过NFZ和TZD（10 microM），Rh123在这些细胞中的积累分别降低至对照的65％和74％。结论是，在Caco-2细胞中NFZ和TZD的转运速率差异不明显。但是，NFZ在临床相关的体内浓度下是P-gp活性的抑制剂，可能具有增加共同施用的化合物（作为转运底物）的生物利用度的潜力。长期口服后在肠道中达到的NFZ和TZD浓度可能会诱导P-gp表达并减少共同给药药物的吸收。

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