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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Pharmacokinetic interaction between nevirapine and nortriptyline in rats: Inhibition of nevirapine metabolism by nortriptyline
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Pharmacokinetic interaction between nevirapine and nortriptyline in rats: Inhibition of nevirapine metabolism by nortriptyline

机译：奈韦拉平与去甲替林之间的药代动力学相互作用：去甲替林对奈韦拉平代谢的抑制作用

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摘要

One of the most frequent comorbidities of HIV infection is depression, with a lifetime prevalence of 22 to 45%. Therefore, it was decided to study a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) and the tricyclic antidepressant nortriptyline (NT). NVP and NT were administered to rats either orally, intraduodenally, or intravenously, and the changes in plasma levels and pharmacokinetic parameters were analyzed. Experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effects of NT on NVP metabolism. NVP plasma concentrations were significantly higher when this drug was coadministered with NT. The maximum plasma concentrations of NVP were increased 2 to 5 times and the total plasma clearance was decreased 7-fold in the presence of NT. However, statistically significant differences in the pharmacokinetic parameters of NT in the absence and presence of NVP were not found. In vitro studies with rat and human hepatic microsomes confirmed the inhibition of NVP hepatic metabolism by NT in a concentration-dependent way, with the inhibition being more intense in the case of rat microsomes. In conclusion, a pharmacokinetic interaction between NVP and NT was detected. This interaction was a consequence of the inhibition of hepatic metabolism of NVP by NT. In vivo human studies are required to evaluate the effects of this interaction on the pharmacokinetics of NVP before it can be taken into account for patients receiving NVP.
机译：HIV感染最常见的合并症之一是抑郁症，终生患病率为22％至45％。因此，决定研究非核苷逆转录酶抑制剂奈韦拉平（NVP）和三环抗抑郁药去甲替林（NT）之间的潜在药代动力学相互作用。口服，十二指肠内或静脉内给大鼠施用NVP和NT，并分析血浆水平和药代动力学参数的变化。进行了大鼠和人肝微粒体的实验，以评估NT对NVP代谢的抑制作用。当该药物与NT并用时，NVP血浆浓度明显更高。在NT存在下，NVP的最大血浆浓度增加了2至5倍，总血浆清除率降低了7倍。然而，在没有和存在NVP的情况下，未发现NT的药代动力学参数具有统计学上的显着差异。用大鼠和人肝微粒体进行的体外研究证实，NT对NVP肝代谢的抑制作用呈浓度依赖性，其中对大鼠微粒体的抑制作用更为强烈。总之，检测到NVP和NT之间的药代动力学相互作用。这种相互作用是NT抑制NVP肝脏代谢的结果。需要进行体内人体研究以评估这种相互作用对NVP药代动力学的影响，然后才能考虑将其用于接受NVP的患者。

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