Geng Ting, Si Haihong, Kang Danyu, Li Yanjing, Huang Wenzhe, Ding Gang, Wang Zhenzhong, Bi Yu'an, Zhang Hong, Xiao Wei
Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China; State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China; China Pharmaceutical University, Nanjing 210009, China.
J Ethnopharmacol. 2015 Nov 4;174:426-36. doi: 10.1016/j.jep.2015.08.035. Epub 2015 Aug 28.
Re Du Ning Injection (RDN), a traditional Chinese medicine injection, is made from the extracts of Lonicerae japonicae flos (LJF), Artemisiae annuae herba (AAH) and Gardeniae fructus (GF). Since last decade, RDN has been widely used in China for the treatment of fever, inflammation, allergy and viral infection.
To elucidate the potential influences of RDN on the activities of four cytochrome P450 (CYP) isozymes in rats (CYP1A2, CYP2C11, CYP2D1 and CYP3A1/2) by "cocktail method".
A sensitive and specific LC-MS method capable of simultaneous quantification of four substrates and their metabolites in rat plasma was developed and validated. Relative activity estimation of four isozymes was carried out by comparing plasma pharmacokinetics of substrates and their metabolites (phenacetin/ paracetamol for CYP1A2, tolbutamide/4-hydroxytolbutamide for CYP2C11, dextromethorphan/ dextrorphan for CYP2D1 and dapsone/N-acetyl dapsone for CYP3A1/2) between control and RDN treatment groups.
Compared with control group, RDN at different levels could increase the total amount of tolbutamide, dextromethorphan and dapsone absorbed into blood, while decrease the total amount of phenacetin absorbed into blood at low and medium dosage and increase it at high dosage.
RDN could inhibit the activities of CYP2C11, CYP2D1 and CYP3A1/2, induce the activity of CYP1A2 at low and medium dosage but inhibit it at high dosage. The results indicated that drug co-administrated with RDN may need dose adjustment.
热毒宁注射液（RDN）是一种中药注射液，由金银花（LJF）、青蒿（AAH）和栀子（GF）的提取物制成。自上世纪九十年代以来，RDN在中国已被广泛用于治疗发热、炎症、过敏和病毒感染。
通过“鸡尾酒法”阐明RDN对大鼠四种细胞色素P450（CYP）同工酶（CYP1A2、CYP2C11、CYP2D1和CYP3A1/2）活性的潜在影响。
建立并验证了一种灵敏且特异的液相色谱-质谱（LC-MS）方法，该方法能够同时定量大鼠血浆中的四种底物及其代谢产物。通过比较对照组和RDN治疗组之间底物及其代谢产物（CYP1A2的非那西丁/对乙酰氨基酚、CYP2C11的甲苯磺丁脲/4-羟基甲苯磺丁脲、CYP2D1的右美沙芬/右啡烷以及CYP3A1/2的氨苯砜/N-乙酰氨苯砜）的血浆药代动力学，对四种同工酶的相对活性进行评估。
与对照组相比，不同剂量的RDN均可增加甲苯磺丁脲、右美沙芬和氨苯砜吸收入血的总量，而低、中剂量时可降低非那西丁吸收入血的总量，高剂量时则增加其吸收入血的总量。
RDN可抑制CYP2C11、CYP2D1和CYP3A1/2的活性，低、中剂量时诱导CYP1A2的活性，但高剂量时抑制其活性。结果表明，与RDN联合用药时可能需要调整剂量。
