Pharmacokinetic herb-drug interactions between Aidi injection and doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma

Yuan Lu,Chunhua Liu,Xiaoqing Zhu,Yongjun Li,Yonglin Wang,Jia Sun,Yueting Li,Jing Huang,Shuai Zhang,Jie Pan,Chuang Cao,Siying Chen,Ting Liu

doi:10.1186/s40360-021-00515-9

Abstract

BackgroundAidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC.MethodsExperimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).ResultsPreadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI.ConclusionsIncreased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.

Highlights

Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC)
Method validation Plasma concentrations of DOX and DOXol were quantified using a validated UPLC-Ultra-performance Liquid Chromatography-Tandem Mass Spectrometry (MS) method previously developed in our laboratory [26]
Sensitivity, selectivity, accuracy, intra- and inter-day precision and stability of the method were validated according to the requirements for bioanalytical methods laid out in the Guidance for Industry Bioanalytical Method Validation Document from the American Food and Drug Administration

Summary

Introduction

Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. Several clinical studies have shown that combining ADI with chemotherapy reduces the toxicity of chemotherapy, enhances clinical efficacy and improves the quality of life of cancer patients [7,8,9]. Many patients use ADI for HCC, before and after treatment with DOX, to reduce toxicity and improve the efficacy of chemotherapy [21, 22] These effects are, insufficient to explain why ADI improves the clinical efficacy of chemotherapy drugs and the mechanism leading to increased efficacy needs to be explained. There have been no reports describing research into pharmacokinetic herb-drug interactions between ADI and DOX and the nature of the interaction remains unknown

Methods

Results

Conclusion