New Research Evaluates Effects of Pregnancy-related Hormones on Hepatic Drug-metabolizing Enzymes
Source:

BioIVT

April 6, 2021

Research provides insight into mechanistic factors that alter hepatic drug disposition during pregnancy

 

BioIVT, a leading provider of research models and services for drug and diagnostic development, today announced that it will be hosting a webinar on April 8 at 11 a.m. ET entitled “Effect of Pregnancy-related Hormones on CYP Induction: Implications for In Vitro ADME-Tox Models.”

“It can be challenging to determine the effects of pregnancy-related hormones on drug pharmacokinetics because pregnancy is usually an exclusion criterion for clinical studies and animal models are not necessarily predictive of human pharmacokinetics. However, a significant number of women need to take at least one medication during their pregnancy and physicians often lack information about how to manage or adjust drug dose recommendations,” said Dr. Chris Black, Senior VP, ADME Tox at BioIVT.

During this webinar, BioIVT Senior Scientist Raju Khatri, MS, PhD, DABT, will discuss his recently published research which shows how pregnancy-related hormones (PRH) are important regulators of hepatic cytochrome P450 (CYP) enzyme expression and function.1 As CYP enzymes play an important role in drug metabolism, altering their expression can change the effectiveness and safety of some drugs.

Using a sandwich-cultured human hepatocyte (SCHH) model, Dr. Khatri’s research team showed that exposure to PRH can significantly increase concentrations of CYP3A4 and other CYPs, resulting in a dose-dependent increase in nifedipine metabolism.1 Nifedipine is a calcium-channel blocker that is often prescribed during pregnancy to manage hypertensive disorder.

“This approach could prove to be a potent addition to conventional in vitro metabolism, toxicity, and disposition studies during drug discovery, and illustrates the caliber of science that Raju brings to our team,” added Dr. Black.

During the webinar, Dr. Khatri will describe how to incorporate PRH effects on drug metabolism into ADME-Tox studies. He will also provide practical tips on how to use a SCHH model for CYP induction studies.

Dr. Khatri earned his PhD in Toxicology at the University of Maryland, Baltimore (UMB), where he focused on Nrf2-mediated drug resistance due to upregulation of drug metabolizing enzymes and efflux transporters. He later studied the effect of PRH on the metabolism of antihypertension drugs at UNC Chapel Hill. At BioIVT, Dr. Khatri leads the study design and implementation of in vitro ADME research, with a focus on CYP metabolism.

BioIVT implements hepatic ADME Tox programs to help biopharmaceutical clients advance their drug discovery programs and prepare IND submissions. The company also provides a unique range of conventional and specialized hepatic products, including LIVERPOOL® and TRANSPORTER CERTIFIED® hepatocytes and the HEPATOPAC® system, a long-term co-culture of primary hepatocytes and fibroblasts used for hepatic safety and metabolism studies and disease models.

Interested persons can register for this complimentary webinar at https://info.bioivt.com/cyp-induction-wbr-reg.

Reference

  1. Khatri et. al. Pregnancy-Related Hormones Increase Nifedipine Metabolism in Human Hepatocytes by Inducing CYP3A4 Expression. J Pharm Sci. September 12, 2020. https://jpharmsci.org/article/S0022-3549(20)30511-6/fulltext#%20

 

About BioIVT

BioIVT is a leading global provider of research models and value-added research services for drug discovery and development. We specialize in control and disease-state biospecimens including human and animal tissues, cell products, blood and other biofluids. Our unmatched portfolio of clinical specimens directly supports precision medicine research and the effort to improve patient outcomes by coupling comprehensive clinical data with donor samples. And as the premier supplier of hepatic products, including hepatocytes and subcellular fractions, BioIVT enables scientists to better understand the pharmacokinetics and drug metabolism of newly discovered compounds and their effects on disease processes. By combining our technical expertise, exceptional customer service, and unparalleled access to biological specimens, BioIVT serves the research community as a trusted partner in elevating science. For more information, please visit www.bioivt.com or follow the company on Twitter @BioIVT.

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