Related Experiment Video

Updated: May 22, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

7.7K

Inhibition Mechanism of Ketamine-Apatinib by CYP2C9 and 3A4: A Prediction of Possible Drug-Drug Interaction

Xiang Zheng1, Haiyan Chen1, Dan Lin2

  • 1Department of Pharmacy, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, China.

Biopharmaceutics & Drug Disposition
|May 21, 2025
PubMed

Insights

Apatinib inhibits ketamine metabolism by affecting key enzymes like CYP2C9 and CYP3A4. This interaction may increase adverse effects in cancer patients, particularly those with poor metabolizer status.

Area of Science:

  • Pharmacology
  • Oncology
  • Drug Metabolism

Background:

  • Cancer pain is prevalent, often managed with drugs like ketamine.
  • Apatinib (VEGFR2 inhibitor) treats gastric cancer but its interaction with ketamine is unknown.
  • Ketamine aids cancer pain relief but has dose-dependent side effects.

Purpose of the Study:

  • To investigate if apatinib affects ketamine metabolism.
  • To determine the inhibitory effects of apatinib on specific cytochrome P450 enzymes.

Main Methods:

  • In vitro assays using CYP2C9 and CYP3A4 isoforms.
  • Molecular docking simulations to assess binding affinities.
  • Analysis of apatinib's inhibitory patterns (noncompetitive, competitive, mixed).

Main Results:

  • Apatinib inhibited ketamine metabolism via CYP2C9 and CYP3A4.
  • Apatinib showed varied inhibition types across different CYP2C9 and CYP3A4 alleles.
  • Molecular docking indicated stronger binding of apatinib to CYP3A4*1 compared to ketamine.

Conclusions:

  • Apatinib interferes with ketamine metabolism, primarily through CYP2C9 and CYP3A4 inhibition.
  • Co-administration may elevate ketamine-related adverse events, especially in poor metabolizers.
  • Further in vivo studies are needed to validate these findings and assess clinical implications.
Keywords:
apatinibcompetitive inhibitioncytochrome P450 proteinsketamine

More Related Videos

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

7.8K
Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

12.7K

Related Concept Videos

Factors Affecting Protein-Drug Binding: Drug Interactions01:23

Factors Affecting Protein-Drug Binding: Drug Interactions

Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
83
Protein-Drug Binding: Mechanism and Kinetics01:16

Protein-Drug Binding: Mechanism and Kinetics

Protein-drug binding refers to the interaction between drugs and proteins within the body. This binding process can occur intracellularly, involving drug interactions with enzymes or receptors within cells, or extracellularly, involving plasma proteins in the blood.
Various forces drive these interactions, including hydrogen bonds, hydrophobic interactions, ionic bonds, electrostatic interactions, and van der Waals forces. These bonds enable drugs to bind to specific sites on proteins,...
222
Combined Effects of Drugs: Antagonism01:30

Combined Effects of Drugs: Antagonism

The combined effects of drugs can result in various interactions, of which an important type is antagonism. Antagonism is a mechanism where one drug inhibits or counteracts the effects of another drug. Antagonism can occur through various means, including receptor binding, allosteric modulation, functional interaction, chemical reactions, and pharmacokinetic processes.
The most common type is receptor antagonism, where one drug acts as an antagonist to block the effects of another drug by...
8.2K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Drug-Receptor Interaction: Antagonist01:28

Drug-Receptor Interaction: Antagonist

An antagonist is a drug that binds strongly to a receptor without activating it. An antagonist prevents other molecules, such as neurotransmitters or hormones, from binding to the receptor and triggering a cellular response. Such interaction effectively hinders the normal physiological processes mediated by the receptor, resulting in various pharmacological effects depending on the specific receptor targeted.
Antagonists can be classified as competitive or noncompetitive based on their...
2.6K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
145