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Background: 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. 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.
Methods: Experimental 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).
Results: Preadministration 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.
Conclusions: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.
Keywords
Pharmacokinetic herb-drug interaction, Hepatocellular carcinoma, Aidi Injection, Doxorubicin, Doxorubicinol, Rat
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CURRENT STATUS: Under Review
The most recent version of this article is available here.
No community comments so far
Editorial decision: Major revision
On 11 Feb, 2021
Review #4 received
Received 31 Jan, 2021
Reviewer #4 agreed
On 29 Jan, 2021
Review #3 received
Received 19 Dec, 2020
Reviewer #3 agreed
On 15 Dec, 2020
Review #2 received
Received 02 Nov, 2020
Reviewer #2 agreed
On 14 Oct, 2020
Reviewer #1 agreed
On 10 Oct, 2020
Review #1 received
Received 10 Oct, 2020
Reviewers invited
Invitations sent on 09 Oct, 2020
Editor assigned
On 29 Sep, 2020
Submission checks complete
On 28 Sep, 2020
Editor invited
On 28 Sep, 2020
Version 3
Posted 21 Sep, 2020
No comments provided
Editorial decision: Minor revision
On 27 Sep, 2020
Review #2 received
Received 25 Sep, 2020
Reviewer #2 agreed
On 22 Sep, 2020
Reviewer #1 agreed
On 19 Sep, 2020
Review #1 received
Received 19 Sep, 2020
Reviewers invited
Invitations sent on 19 Sep, 2020
Editor assigned
On 17 Sep, 2020
Submission checks complete
On 16 Sep, 2020
Editor invited
On 16 Sep, 2020
No comments provided
Editorial decision: Major revision
On 06 Sep, 2020
Review #3 received
Received 01 Sep, 2020
Review #2 received
Received 25 Aug, 2020
Reviewer #2 agreed
On 17 Aug, 2020
Reviewer #3 agreed
On 17 Aug, 2020
Reviewers invited
Invitations sent on 12 Aug, 2020
Reviewer #1 agreed
On 12 Aug, 2020
Review #1 received
Received 12 Aug, 2020
Editor assigned
On 10 Aug, 2020
Submission checks complete
On 09 Aug, 2020
Editor invited
On 09 Aug, 2020
No comments provided
Editorial decision: Major revision
On 08 Jul, 2020
Review #2 received
Received 01 Jul, 2020
Reviewer #3 agreed
On 22 Jun, 2020
Reviewer #4 agreed
On 22 Jun, 2020
Review #3 received
Received 22 Jun, 2020
Review #1 received
Received 13 Jun, 2020
Reviewers invited
Invitations sent on 08 Jun, 2020
Reviewer #1 agreed
On 08 Jun, 2020
Reviewer #2 agreed
On 08 Jun, 2020
Editor assigned
On 27 May, 2020
Submission checks complete
On 26 May, 2020
Editor invited
On 26 May, 2020
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A new preprint design is coming!
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This preprint is under consideration at BMC Pharmacology and Toxicology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
The most recent version of this article is available here.
No community comments so far
Editorial decision: Major revision
On 11 Feb, 2021
Review #4 received
Received 31 Jan, 2021
Reviewer #4 agreed
On 29 Jan, 2021
Review #3 received
Received 19 Dec, 2020
Reviewer #3 agreed
On 15 Dec, 2020
Review #2 received
Received 02 Nov, 2020
Reviewer #2 agreed
On 14 Oct, 2020
Reviewer #1 agreed
On 10 Oct, 2020
Review #1 received
Received 10 Oct, 2020
Reviewers invited
Invitations sent on 09 Oct, 2020
Editor assigned
On 29 Sep, 2020
Submission checks complete
On 28 Sep, 2020
Editor invited
On 28 Sep, 2020
Version 3
Posted 21 Sep, 2020
No comments provided
Editorial decision: Minor revision
On 27 Sep, 2020
Review #2 received
Received 25 Sep, 2020
Reviewer #2 agreed
On 22 Sep, 2020
Reviewer #1 agreed
On 19 Sep, 2020
Review #1 received
Received 19 Sep, 2020
Reviewers invited
Invitations sent on 19 Sep, 2020
Editor assigned
On 17 Sep, 2020
Submission checks complete
On 16 Sep, 2020
Editor invited
On 16 Sep, 2020
No comments provided
Editorial decision: Major revision
On 06 Sep, 2020
Review #3 received
Received 01 Sep, 2020
Review #2 received
Received 25 Aug, 2020
Reviewer #2 agreed
On 17 Aug, 2020
Reviewer #3 agreed
On 17 Aug, 2020
Reviewers invited
Invitations sent on 12 Aug, 2020
Reviewer #1 agreed
On 12 Aug, 2020
Review #1 received
Received 12 Aug, 2020
Editor assigned
On 10 Aug, 2020
Submission checks complete
On 09 Aug, 2020
Editor invited
On 09 Aug, 2020
No comments provided
Editorial decision: Major revision
On 08 Jul, 2020
Review #2 received
Received 01 Jul, 2020
Reviewer #3 agreed
On 22 Jun, 2020
Reviewer #4 agreed
On 22 Jun, 2020
Review #3 received
Received 22 Jun, 2020
Review #1 received
Received 13 Jun, 2020
Reviewers invited
Invitations sent on 08 Jun, 2020
Reviewer #1 agreed
On 08 Jun, 2020
Reviewer #2 agreed
On 08 Jun, 2020
Editor assigned
On 27 May, 2020
Submission checks complete
On 26 May, 2020
Editor invited
On 26 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Background: 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. 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.
Methods: Experimental 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).
Results: Preadministration 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.
Conclusions: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
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