Time-dependent Inhibition of Piperine and its Impact on the Metabolism of Carbamazepine
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摘要Piperine, the major bioactive component from black pepper, is associated with beneficial effects on central nervous system, such as anti-epilepsy1. It also has modulation effects on drug metabolic enzyme thus may alter the concentration of many therapeutic agents. Carbamazepine (CBZ) is a frontline therapy for epilepsy with narrow therapeutic index. Higher CBZ concentration were found after co-administration with piperine in human, which may due to the inhibition of CBZ metabolism2. The present study was proposed to examine the underlying pharmacokinetics-based mechanisms of this interaction.
The effect of piperine on phase I hepatic metabolism of CBZ was examined using rat and human liver microsome. Time-dependent inhibition potential was further tested by pre-incubation of piperine with microsome. Ex-vivo approach was applied by given oral administration of at 3.5 mg/kg and 35 mg/kg piperine once daily for 2 weeks to male Sprague-Dawley rats. On last day of treatment, rat livers were collected and rat liver microme were prepared. The microsome activity, hepatic mRNA and protein expression of CYP isozymes were determined and compared between different treatment groups.
Piperine showed inhibitory effect on CBZ metabolism with IC50 of 9.20±1.36 μM and 10.00±1.22 μM in rat and human liver microsome, respectively. Pre-incubation of piperine with microsome could result in further inhibition indicating the time-dependent inhibition. Ex-vivo studies showed piperine at 35 mg/kg could inhibit the microsome activity in CBZ metabolism while not affect mRNA or protein expression of genes involved in CBZ metabolism.
Therefore, piperine could inhibit the CBZ metabolism through time-dependent inhibition, which is not related to down-regulation of gene involved in CBZ metabolism. The inhibition effect of piperine was significant after multiple-dosing which warrants further investigation.
出版社接受日期04.07.2018
著者Tianjing REN, Mengbi YANG, Min XIAO, Zhong ZUO
會議名稱Globalization of Pharmaceutics Education Network (GPEN) Meeting 2018
會議開始日26.09.2018
會議完結日29.09.2018
會議地點Singapore
會議國家/地區新加坡
出版年份2018
月份9
語言美式英語
關鍵詞Piperine, carbamazepine, pharmacokinetics, interaction, metabolism

上次更新時間 2020-21-04 於 17:02