CYP3A4

CYP3A is a subfamily of cytochrome P450 enzymes that are responsible for metabolizing a vast majority of endogenous and exogenous substances in the body, including hundreds of drugs. CYP3A enzymes are predominantly expressed in the liver and the intestines and are responsible for metabolizing over 50% of drugs currently in clinical use, including statins, immunosuppressants, antivirals, and many others. Induction or inhibition of CYP3A activity can alter the plasma concentrations and pharmacological effects of co-administered drugs. Therefore, assessing CYP3A activity through induction assays or monitoring CYP3A interactions is important in clinical practice to ensure optimal drug therapy and minimize the risk of adverse effects.

CYP3A consists of four main CYP3A isoforms in humans: CYP3A4, CYP3A5, CYP3A7, and CYP3A43. Among the CYP3A isoforms, CYP3A4 is the most abundant and extensively studied isoform in terms of drug metabolism and interactions.

Table 1. Some CYP3A substrates, inducers and inhibitors.

CYP3A Induction Assay Service

Creative Biolabs specializes in providing a comprehensive CYP induction assay service. Our experts assess the induction potential of compounds on CYP3A by analyzing enzyme activity using the CYP3A substrate. This service utilizes HPLC-MS/MS methods to detect the corresponding metabolite, providing valuable insights into the induction potential of CYP3A enzymes.

Midazolam is extensively used as a prototypic substrate for assessing CYP3A enzyme activity. The metabolism of Midazolam by CYP3A enzymes results in the formation of 1'-hydroxymidazolam, a primary metabolite that serves as a reliable biomarker for CYP3A activity. This process is often evaluated through specialized techniques like HPLC-MS/MS, which allows for the accurate detection and quantification of the metabolite. By offering CYP3A induction assay services utilizing Midazolam as a substrate for enzyme activity testing, our lab ensures precise and reliable results for evaluating CYP3A enzyme induction potential.

Besides, our scientists also use qRT-PCR technology to detect mRNA levels of the CYP3A gene. The assay can be used to screen potential drug candidates for their ability to induce CYP3A expression, which can help predict their potential for drug-drug interactions.

Please let us know if you would like more information or if you are interested in utilizing our CYP3A induction assay service.

Highlights

• Comprehensive gene expression analysis and enzyme activity detection
• Both positive and negative controls included
• Guidance and support are provided by our team of experienced scientists to ensure the success of your project.
• Flexible assay design to accommodate specific requirements

Support Data

Data 1: CYP3A4 induction by calcitriol was performed using a CYP3A4 activity test. The calcitriol induced CYP2B6 activity in HepaRG cells in a dose-dependent manner.

Host cell: Human hepatocytes or HepaRG cells

Substrate: Testosterone

Detection of metabolite: 6β-hydroxytestosterone

Detection method: LC-MS/MS

Fig.1 CYP3A4 activity measurement.^1,2

References

1. Chae, Yoon-Jee, et al. "Pharmacokinetic estimation models-based approach to predict clinical implications for CYP induction by calcitriol in human cryopreserved hepatocytes and HepaRG cells." Pharmaceutics 13.2 (2021): 181.
2. Distributed under Open Access license CC BY 4.0, without modification.

For Research Use Only | Not For Clinical Use