A Short Exploration of Selected Sensitive CYP3A4 Substrates (Probe Drug)

Author(s): Sarvesh Sabarathinam, Thangavel M. Vijayakumar*

Journal Name: Drug Metabolism Letters

Volume 14 , Issue 1 , 2021


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Graphical Abstract:


Abstract:

Background: CYP450 enzymes in the liver have a significant role in the metabolism of xenobiotics. Probe drug strategy is broadly used to evaluate the pharmacodynamic and pharmacokinetic drug/ herb-drug interactions/ food-drug interactions. Probe drugs reveal the exact pathway of drug metabolism in the liver by their targeted tractability property. The CYP3A4 isoenzyme metabolizes the majority of the drugs (65%).

Methods: The characteristics of targeted probe drugs were observed from the admetSAR (version2) online database.

Results: Midazolam is widely used as a probe drug because of its peculiar character. Midazolam affirms the accurate and consistent prediction of pharmacokinetic mediated drug interactions even in nanogram concentrations with or without a potent CYP3A inhibitor. Remarkably, midazolam is used as a CYP3A4 substrate in the majority of in vivo studies.

Conclusion: It is concluded that midazolam shows a good response in all clinical studies because of its lesser half-life and bioavailability when compared with other probe drugs.

Keywords: Probe drug, CYP3A4, midazolam, drug interactions, substrates, inhibitor, CAM.

[1]
Sarvesh, S.; Koushik Muthu Raja, M.; Rajanandh, M.G.; Seenivasan, P. Prevalence and pattern of usage of complementary and alternative medicine among south Indian asthma patients in a tertiary care hospital. Complement. Ther. Clin. Pract., 2018, 30(30), 103-108.
[http://dx.doi.org/10.1016/j.ctcp.2017.12.016] [PMID: 29389468]
[2]
Na, D.H.; Ji, H.Y.; Park, E.J.; Kim, M.S.; Liu, K-H.; Lee, H.S. Evaluation of metabolism-mediated herb-drug interactions. Arch. Pharm. Res., 2011, 34(11), 1829-1842.
[http://dx.doi.org/10.1007/s12272-011-1105-0] [PMID: 22139684]
[3]
Hu, S.X.; Mazur, C.A.; Feenstra, K.L. Assessment of inhibition of bovine hepatic cytochrome P450 by 43 commercial bovine medicines using a combination of in vitro assays and pharmacokinetic data from the literature. Drug Metab. Lett., 2019, 13(2), 123-131.
[http://dx.doi.org/10.2174/1872312813666191120094649] [PMID: 31750810]
[4]
Kaushik, R.; Khan, S.; Sharma, M.; Hemalatha, S.; Mueed, Z.; Nitesh, K. Poddar. Role of cytochrome p450 in prostate cancer and its therapy. Curr. Enzym. Inhib., 2020, 16, 63.
[http://dx.doi.org/10.2174/1573408016666200218122044]
[5]
Giri, P.; Patel, H.; Srinivas, N.R. Use of cocktail probe drugs for indexing cytochrome P450 enzymes in clinical pharmacology studies - review of case studies. Drug Metab. Lett., 2019, 13(1), 3-18.
[http://dx.doi.org/10.2174/1872312812666181119154734] [PMID: 30451124]
[6]
Halama, B.; Hohmann, N.; Burhenne, J.; Weiss, J.; Mikus, G.; Haefeli, W.E. A nanogram dose of the CYP3A probe substrate midazolam to evaluate drug interactions. Clin. Pharmacol. Ther., 2013, 93(6), 564-571.
[http://dx.doi.org/10.1038/clpt.2013.27] [PMID: 23511711]
[7]
Yang, Hongbin; Sun, Lixia; Wang, Zhuang; Li, Weihua; Liu, Guixia; Tang, Yun. ADMETopt: A Web Server for ADMET Optimization in Drug Design via Scaffold Hopping J. Chem. Inf. Model., 2018, 58(10), 2051-2056.
[8]
Fisher, C.D.; Lickteig, A.J.; Augustine, L.M.; Ranger-Moore, J.; Jackson, J.P.; Ferguson, S.S.; Cherrington, N.J. Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab. Dispos., 2009, 37(10), 2087-2094.
[http://dx.doi.org/10.1124/dmd.109.027466] [PMID: 19651758]
[9]
Teo, Y.L.; Ho, H.K.; Chan, A. Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations. Br. J. Clin. Pharmacol., 2015, 79(2), 241-253.
[http://dx.doi.org/10.1111/bcp.12496] [PMID: 25125025]


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Article Details

VOLUME: 14
ISSUE: 1
Year: 2021
Published on: 11 August, 2020
Page: [2 - 4]
Pages: 3
DOI: 10.2174/1872312814666200811110024
Price: $65

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