Ouyang Huizi, Shen Jiayuan, Huang Xuhua, Ma Wenjuan, Jia Qi, Yao Guangzhe, Tang Zhidan, Zhang Dandan, Sun Mengjie, Teye Azietaku John, Hao Jia, Gao Xiumei, Chang Yanxu, He Jun
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Evid Based Complement Alternat Med. 2019 Sep 23;2019:5242605. doi: 10.1155/2019/5242605. eCollection 2019.
Naoxintong capsule (NXT), a prescribed Chinese medicine, has been used clinically for more than 20 years and is widely received by patients. We determined five probe drugs, namely, omeprazole (CYP2C19), midazolam (CYP3A4), phenacetin (CYP1A2), tolbutamide (CYP2C9), and dextromethorphan (CYP2D6) to study the potential influences of NXT on the activities of CYP enzymes and assessed the pharmacokinetics effect of NXT on metoprolol tartrate in rat plasma. The study showed that AUC and AUC of midazolam (CYP3A4) in NXT coadministration group (283.7 ± 65.2 h·ng·mL and 292.0 ± 75.1 h·ng·mL in group B; 295.7 ± 62.7 h·ng·mL and 299.5 ± 60.0 h·ng·mL in group C) were significantly decreased as compared to another group (416.8 ± 82.3 h·ng·mL and 424.9 ± 77.9 h·ng·mL in group A), while that of dextromethorphan (CYP2D6) showed an opposite tendency (540.7 ± 119.7 h·ng·mL and 595.3 ± 122.2 h·ng·mL in group A, 760.6 ± 184.9 h·ng·mL and 788.7 ± 211.0 h·ng·mL in group B, and 734.3 ± 118.5 h·ng·mL and 757.2 ± 105.4 h·ng·mL in group C). Moreover, NXT preadministration can enhance the metabolism of metoprolol tartrate and reduce the metabolism of O-demethylmetoprolol. The results indicated that NXT had potential effects in inducing CYP3A4 and inhibiting CYP2D6 in the metabolism of metoprolol tartrate. It suggests that patients who coadministered NXT and metoprolol tartrate should be advised of potential herb-drug interactions (HDIs) to reduce therapeutic failure or accelerated toxicity of conventional drug treatment.
脑心通胶囊（NXT）是一种处方药，已在临床应用20多年，深受患者欢迎。我们确定了5种探针药物，即奥美拉唑（CYP2C19）、咪达唑仑（CYP3A4）、非那西丁（CYP1A2）、甲苯磺丁脲（CYP2C9）和右美沙芬（CYP2D6），以研究NXT对CYP酶活性的潜在影响，并评估NXT对大鼠血浆中酒石酸美托洛尔药代动力学的影响。研究表明，NXT联合给药组中咪达唑仑（CYP3A4）的AUC和AUC（B组为283.7±65.2 h·ng·mL和292.0±75.1 h·ng·mL；C组为295.7±62.7 h·ng·mL和299.5±60.0 h·ng·mL）与另一组（A组为416.8±82.3 h·ng·mL和424.9±77.9 h·ng·mL）相比显著降低，而右美沙芬（CYP2D6）则呈现相反趋势（A组为540.7±119.7 h·ng·mL和595.3±122.2 h·ng·mL，B组为760.6±184.9 h·ng·mL和788.7±211.0 h·ng·mL，C组为734.3±118.5 h·ng·mL和757.2±105.4 h·ng·mL）。此外，NXT预先给药可增强酒石酸美托洛尔的代谢并减少O-去甲基美托洛尔的代谢。结果表明，NXT在酒石酸美托洛尔代谢中具有诱导CYP3A4和抑制CYP2D6的潜在作用。这表明，同时服用NXT和酒石酸美托洛尔的患者应被告知潜在的草药-药物相互作用（HDIs），以减少治疗失败或传统药物治疗的加速毒性。
