Common Approaches of Cytochrome P450 (CYP) Induction Assays
International Blood Research & Reviews,
Page 6-14
DOI:
10.9734/ibrr/2023/v14i1297
Abstract
The induction of enzymes is a defensive mechanism for some xenobiotics, but it may alter the drug's safety and efficacy by altering the activity of metabolic enzymes. One of the major families of enzymes involved in phase I metabolism is Cytochrome P450 (CYP) enzymes which may get induced by certain drugs. Concomitant administration of drugs due to chronic disease or polypharmacy, inducers among them may cause toxicity or reduce the plasma concentration at a sub-therapeutic level. This is one of the dangerous types of drug-drug interactions, but predictable & preventable. The CYPs get induced by three nuclear receptors, including the aryl hydrocarbon receptor (AhR); constitutive androstane receptor (CAR); the pregnane X receptor (PXR). Without identification during drug development, enzyme induction phenomenon of a new drug molecule may get noticed only during pharmacovigilance. Though, this CYP induction may not be a barrier for drug development, it may cause possible DDI and treatment failure. According to FDA guidelines, pharmaceutical industries adopted In-vitro, Ex-vivo and In-vivo techniques based on different developmental stages. The results are also interpreted based on regulatory bodies guidelines. For In-vitro assay best accepted method is using primary hepatocytes either fresh or cryopreserved, for Ex-vivo liver slices of different species and in-vivo, clinical investigations are the extreme option. This paper reviews current industry approaches of CYP induction assays to evaluate potentiality for a new drug molecule as an inducer.
Keywords:
- Cytochrome P450
- CYPs
- DDI
- induction
- FDA
- EMA
- PK
How to Cite
Ghosh, R., Nayan, M. I. H., Mitu, M. M., & Nandi, T. (2023). Common Approaches of Cytochrome P450 (CYP) Induction Assays. International Blood Research & Reviews, 14(1), 6-14. https://doi.org/10.9734/ibrr/2023/v14i1297
References
Zhang L, Zhang YD, Zhao P, Huang S-M. Predicting drug–drug interactions: An FDA perspective. The AAPS Journal. 2009; 11(2):300-6.
Zheng WY, Richardson L, Li L, Day R, Westbrook J, Baysari M. Drug-drug interactions and their harmful effects in hospitalised patients: A systematic review and meta-analysis. European Journal of Clinical Pharmacology. 2018;74(1):15-27.
Diksis N, Melaku T, Assefa D, Tesfaye A. Potential drug–drug interactions and associated factors among hospitalized cardiac patients at Jimma University Medical Center, Southwest Ethiopia. SAGE Open Medicine. 2019; 7:2050312119857353.
Nandi T. Importance of sufficient time-points for efficient pharmacokinetic (PK) compartmental modeling. International Journal of Applied Pharmaceutics. 2023; 15(1):87-92.
Palleria C, Di Paolo A, Giofrè C, Caglioti C, Leuzzi G, Siniscalchi A, et al. Pharmacokinetic drug-drug interaction and their implication in clinical management. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2013;18(7):601.
Niu J, Straubinger RM, Mager DE. Pharmacodynamic Drug–drug interactions. Clinical Pharmacology & Therapeutics. 2019;105(6):1395-406.
Ayenew W, Asmamaw G, Issa A. Prevalence of potential drug-drug interactions and associated factors among outpatients and inpatients in Ethiopian hospitals: A systematic review and meta-analysis of observational studies. BMC Pharmacology and Toxicology. 2020; 21(1):1-13.
Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug-drug interactions: Population database analysis 1995–2010. BMC Medicine. 2015;13(1): 1-10.
Johnell K, Klarin I. The relationship between number of drugs and potential drug-drug interactions in the elderly. Drug Safety. 2007;30(10):911-8.
Peng Y, Cheng Z, Xie F. Evaluation of pharmacokinetic drug–drug interactions: A review of the mechanisms, in vitro and in silico approaches. Metabolites. 2021; 11(2):75.
Strandell J, Wahlin S. Pharmacodynamic and pharmacokinetic drug interactions reported to VigiBase, the WHO global individual case safety report database. European Journal of Clinical Pharmacology. 2011;67(6):633-41.
Nandi T, Korzekwa K, Nagar S, editors. In-vitro enzyme kinetics of NCD metabolism to DNCD in RLM and RIM. Research Recognition Day; 2022; Temple University School of Pharmacy; 2022.
Nandi T, Korzekwa K, Nagar S, editors. In vitro midazolam metabolism and CYP atypical kinetics in SD rat microsomes. Research Recognition Day; 2021; Temple University School of Pharmacy; 2021.
Zhao M, Ma J, Li M, Zhang Y, Jiang B, Zhao X, et al. Cytochrome P450 enzymes and drug metabolism in humans. International Journal of Molecular Sciences. 2021;22(23):12808.
Hakkola J, Hukkanen J, Turpeinen M, Pelkonen O. Inhibition and induction of CYP enzymes in humans: An update. Archives of Toxicology. 2020;94(11):3671-722.
Lynch T, Neff AP. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. American Family Physician. 2007;76(3): 391-6.
Lin JH. CYP induction-mediated drug interactions: In vitro assessment and clinical implications. Pharmaceutical Research. 2006;23(6):1089-116.
Palatini P, De Martin S. Pharmacokinetic drug interactions in liver disease: An update. World Journal of Gastroenterology. 2016;22(3):1260.
Hewitt N, Lecluyse E, Ferguson S. Induction of hepatic cytochrome P450 enzymes: Methods, mechanisms, recommendations, and in vitro–in vivo correlations. Xenobiotica. 2007;37(10-11):1196-224.
Fuhr U. Induction of Drug metabolising enzymes. Clinical Pharmacokinetics. 2000; 38(6):493-504.
Graham MJ, Lake BG. Induction of drug metabolism: Species differences and toxicological relevance. Toxicology. 2008;254(3):184-91.
Liguori MJ, Lee C-H, Liu H, Ciurlionis R, Ditewig AC, Doktor S, et al. AhR activation underlies the CYP1A autoinduction by A-998679 in rats. Frontiers in Genetics. 2012;3:213.
Pelkonen O, Turpeinen M, Hakkola J, Honkakoski P, Hukkanen J, Raunio H. Inhibition and induction of human cytochrome P450 enzymes: Current status. Archives of Toxicology. 2008;82(10):667-715.
Sinz M, Wallace G, Sahi J. Current industrial practices in assessing CYP450 enzyme induction: Preclinical and clinical. The AAPS Journal. 2008;10(2):391-400.
Hakkola J, Bernasconi C, Coecke S, Richert L, Andersson TB, Pelkonen O. Cytochrome P450 induction and xeno‐sensing receptors pregnane X receptor, constitutive androstane receptor, aryl hydrocarbon receptor and peroxisome proliferator‐activated receptor α at the crossroads of toxicokinetics and toxicodynamics. Basic & Clinical Pharmacology & Toxicology. 2018;123: 42-50.
Muangmoonchai R, Smirlis D, Wong S-C, Edwards M, Phillips IR, Shephard EA. Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor Constitutive Androstane Receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1. Biochemical Journal. 2001;355(1):71-8.
Wyen C, Hendra H, Siccardi M, Platten M, Jaeger H, Harrer T, et al. Cytochrome P450 2B6 (CYP2B6) and Constitutive Androstane Receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens. Journal of Antimicrobial Chemotherapy. 2011;66(9):2092-8.
Yang H, Wang H. Signaling control of the Constitutive Androstane Receptor (CAR). Protein & cell. 2014;5(2):113-23.
Smutny T, Mani S, Pavek P. Post-translational and post-transcriptional modifications of Pregnane X Receptor (PXR) in regulation of the cytochrome P450 superfamily. Current Drug Metabolism. 2013;14(10):1059-69.
Coumoul X, Diry M, Barouki R. PXR-dependent induction of human CYP3A4 gene expression by organochlorine pesticides. Biochemical Pharmacology. 2002;64(10):1513-9.
Wei Y, Tang C, Sant V, Li S, Poloyac SM, Xie W. A molecular aspect in the regulation of drug metabolism: Does PXR-induced enzyme expression always lead to functional changes in drug metabolism? Current Pharmacology Reports. 2016; 2(4):187-92.
Pondugula SR, Dong H, Chen T. Phosphorylation and protein–protein interactions in PXR-mediated CYP3A repression. Expert Opinion on Drug Metabolism & Toxicology. 2009;5(8): 861-73.
Percha B, Altman RB. Informatics confronts drug–drug interactions. Trends in Pharmacological Sciences. 2013;34(3): 178-84.
Zhao L, Au JL-S, Wientjes MG. Comparison of methods for evaluating drug-drug interaction. Frontiers in Bioscience (Elite edition). 2010;2:241.
Hewitt NJ, de Kanter R, LeCluyse E. Induction of Drug metabolizing enzymes: A survey of in vitro methodologies and interpretations used in the pharmaceutical industry—do they comply with FDA recommendations? Chemico-Biological Interactions. 2007;168(1):51-65.
Brandon EF, Raap CD, Meijerman I, Beijnen JH, Schellens JH. An update on in vitro test methods in human hepatic drug biotransformation research: Pros and cons. Toxicology and Applied Pharmacology. 2003;189(3):233-46.
Martignoni M, de Kanter R, Grossi P, Mahnke A, Saturno G, Monshouwer M. An in vivo and in vitro comparison of CYP induction in rat liver and intestine using slices and quantitative RT-PCR. Chemico-Biological Interactions. 2004;151(1):1-11.
Pearen MA, Lim HK, Gratte FD, Fernandez-Rojo MA, Nawaratna SK, Gobert GN, et al. Murine precision-cut liver slices as an ex vivo model of liver biology. JoVE (Journal of Visualized Experiments). 2020(157):e60992.
Bernasconi C, Pelkonen O, Andersson TB, Strickland J, Wilk-Zasadna I, Asturiol D, et al. Validation of in vitro methods for human cytochrome P450 enzyme induction: Outcome of a multi-laboratory study. Toxicology in Vitro. 2019;60:212-28.
Grover GS, Brayman TG, Voorman RL, Ware JA. Development of in vitro methods to predict induction of CYP1A2 and CYP3A4 in humans. Assay and Drug Development Technologies. 2007;5(6): 793-804.
Lu C, Di L. In vitro and in vivo methods to assess pharmacokinetic drug–drug interactions in drug discovery and development. Biopharmaceutics & Drug Disposition. 2020;41(1-2):3-31.
Raucy J, Warfe L, Yueh M-F, Allen SW. A cell-based reporter gene assay for determining induction of CYP3A4 in a high-volume system. Journal of Pharmacology and Experimental Therapeutics. 2002; 303(1):412-23.
Lübberstedt M, Müller-Vieira U, Mayer M, Biemel KM, Knöspel F, Knobeloch D, et al. HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in vitro. Journal of Pharmacological and Toxicological Methods. 2011;63(1):59-68.
Zuo R, Li F, Parikh S, Cao L, Cooper KL, Hong Y, et al. Evaluation of a novel renewable hepatic cell model for prediction of clinical CYP3A4 induction using a correlation-based relative induction score approach. Drug Metabolism and Disposition. 2017;45(2):198-207.
Gomez-Lechon M, Donato M, Lahoz A, Castell J. Cell lines: A tool for in vitro drug metabolism studies. Current Drug Metabolism. 2008;9(1):1-11.
Ripp SL, Mills JB, Fahmi OA, Trevena KA, Liras JL, Maurer TS, et al. Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metabolism and Disposition. 2006; 34(10):1742-8.
Aninat C, Piton A, Glaise D, Le Charpentier T, Langouët S, Morel F, et al. Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells. Drug Metabolism and Disposition. 2006;34(1):75-83.
LeCluyse EL, Alexandre E, Hamilton GA, Viollon-Abadie C, Coon DJ, Jolley S, et al. Isolation and culture of primary human hepatocytes. Basic Cell Culture Protocols: Springer; 2005. p. 207-29.
Bulutoglu B, Rey-Bedón C, Mert S, Tian L, Jang Y-Y, Yarmush ML, et al. A comparison of hepato-cellular in vitro platforms to study CYP3A4 induction. PloS One. 2020;15(2):e0229106.
Luo G, Cunningham M, Kim S, Burn T, Lin J, Sinz M, et al. CYP3A4 induction by drugs: Correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metabolism and Disposition. 2002;30(7): 795-804.
Prueksaritanont T, Chu X, Gibson C, Cui D, Yee KL, Ballard J, et al. drug–drug interaction studies: Regulatory guidance and an industry perspective. The AAPS Journal. 2013;15(3):629-45.
Gowing G, Svendsen S, Svendsen CN. Ex vivo gene therapy for the treatment of neurological disorders. Prog Brain Res. 2017;230:99-132. Epub 20170117.
DOI: 10.1016/bs.pbr.2016.11.003. PubMed PMID: 28552237.
XenoTech. Ex Vivo Enzyme Induction Studies: Xeno Tech; 2022.
Available:https://www.xenotech.com/preclinical-drug-development/in-vitro-studies/enzyme-induction/ex-vivo/
Access on 2022 25 December
Surry DD, Meneses-Lorente G, Heavens R, Jack A, Evans DC. Rapid determination of rat hepatocyte mRNA induction potential using oligonucleotide probes for CYP1A1, 1A2, 3A and 4A1. Xenobiotica. 2000; 30(5):441-56.
DOI: 10.1080/004982500237460. PubMed PMID: 10875679
Baldwin SJ, Bramhall JL, Ashby CA, Yue L, Murdock PR, Hood SR, et al. Cytochrome P450 gene induction in rats ex vivo assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (Taq Man). Drug Metab Dispos. 2006;34(6):1063-9. Epub 20060310.
DOI: 10.1124/dmd.105.008185. PubMed PMID: 16531474.
Gibson UE, Heid CA, Williams PM. A novel method for real time quantitative RT-PCR. Genome Res. 1996;6(10):995-1001.
DOI: 10.1101/gr.6.10.995 PubMed PMID: 8908519.
Godfrey TE, Kelly LA. Development of quantitative reverse transcriptase PCR assays for measuring gene expression. Methods Mol Biol. 2005;291:423-45.
DOI: 10.1385/1-59259-840-4:423 PubMed PMID: 15502240
Bustin SA. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000;25(2):169-93.
DOI: 10.1677/jme.0.0250169 PubMed PMID: 11013345
Ginzinger DG. Gene quantification using real-time quantitative PCR: An emerging technology hits the mainstream. Exp Hematol. 2002;30(6):503-12.
DOI: 10.1016/s0301-472x(02)00806-8 PubMed PMID: 12063017
Gaedigk A, Freeman N, Hartshorne T, Riffel AK, Irwin D, Bishop JR, et al. SNP genotyping using TaqMan technology: The CYP2D6*17 assay conundrum. Sci Rep. 2015;5:9257. Epub 20150319.
DOI: 10.1038/srep09257 PubMed PMID: 25788121; PubMed Central PMCID: PMCPMC4365394
Jin SE, Ha H, Seo CS, Shin HK, Jeong SJ. Expression of cytochrome P450s in the liver of rats administered with socheongryong-tang, a traditional herbal formula. Pharmacogn Mag. 2016; 12(47):211-8.
DOI: 10.4103/0973-1296.186340 PubMed PMID: 27601852; PubMed Central PMCID: PMCPMC4989797
Pan J, Xiang Q, Renwick AB, Price RJ, Ball SE, Kao J, et al. Use of a quantitative real-time reverse transcription-polymerase chain reaction method to study the induction of CYP1A, CYP2B and CYP4A forms in precision-cut rat liver slices. Xenobiotica. 2002;32(9):739-47.
DOI:10.1080/00498250210147115 PubMed PMID: 12396271
Medhurst AD, Harrison DC, Read SJ, Campbell CA, Robbins MJ, Pangalos MN. The use of TaqMan RT-PCR assays for semiquantitative analysis of gene expression in CNS tissues and disease models. J Neurosci Methods. 2000; 98(1):9-20.
DOI: 10.1016/s0165-0270(00)00178-3 PubMed PMID: 10837866
nanoString. nCounter® Analysis Systems Overview: Nano String Technology; 2022.
Available:https://nanostring.com/products/ncounter-analysis-system/ncounter-systems-overview/.
Access on 2022 25 December
Klein K, Thomas M, Winter S, Nussler AK, Niemi M, Schwab M, et al. PPARA: A novel genetic determinant of CYP3A4 In vitro and In vivo. Clinical Pharmacology & Therapeutics. 2012;91(6):1044-52.
Palamanda JR, Kumari P, Murgolo N, Benbow L, Lin X, Nomeir AA. Evaluation of CYP1A1 and CYP2B1/2 m-RNA induction in rat liver slices using the Nano String technology: A novel tool for drug discovery lead optimization. Drug Metab Lett. 2009;3(3):171-5. Epub 20090801.
DOI: 10.2174/187231209789352094 PubMed PMID: 19702544
Martignoni M, De Kanter R, Grossi P, Saturno G, Barbaria E, Monshouwer M. An In vivo and In vitro comparison of CYP gene induction in mice using liver slices and quantitative RT-PCR. Toxicology in vitro. 2006;20(1):125-31.
Martignoni M, Groothuis GM, de Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opinion on Drug Metabolism & Toxicology. 2006;2(6):875-94.
Ohno Y, Hisaka A, Ueno M, Suzuki H. General framework for the prediction of oral drug interactions caused by CYP3A4 induction from In vivo information. Clinical Pharmacokinetics. 2008;47(10): 669-80.
Pelkonen O. Human CYPs: In vivo and clinical aspects. Drug Metabolism Reviews. 2002;34(1-2):37-46.
Zheng WY, Richardson L, Li L, Day R, Westbrook J, Baysari M. Drug-drug interactions and their harmful effects in hospitalised patients: A systematic review and meta-analysis. European Journal of Clinical Pharmacology. 2018;74(1):15-27.
Diksis N, Melaku T, Assefa D, Tesfaye A. Potential drug–drug interactions and associated factors among hospitalized cardiac patients at Jimma University Medical Center, Southwest Ethiopia. SAGE Open Medicine. 2019; 7:2050312119857353.
Nandi T. Importance of sufficient time-points for efficient pharmacokinetic (PK) compartmental modeling. International Journal of Applied Pharmaceutics. 2023; 15(1):87-92.
Palleria C, Di Paolo A, Giofrè C, Caglioti C, Leuzzi G, Siniscalchi A, et al. Pharmacokinetic drug-drug interaction and their implication in clinical management. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2013;18(7):601.
Niu J, Straubinger RM, Mager DE. Pharmacodynamic Drug–drug interactions. Clinical Pharmacology & Therapeutics. 2019;105(6):1395-406.
Ayenew W, Asmamaw G, Issa A. Prevalence of potential drug-drug interactions and associated factors among outpatients and inpatients in Ethiopian hospitals: A systematic review and meta-analysis of observational studies. BMC Pharmacology and Toxicology. 2020; 21(1):1-13.
Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug-drug interactions: Population database analysis 1995–2010. BMC Medicine. 2015;13(1): 1-10.
Johnell K, Klarin I. The relationship between number of drugs and potential drug-drug interactions in the elderly. Drug Safety. 2007;30(10):911-8.
Peng Y, Cheng Z, Xie F. Evaluation of pharmacokinetic drug–drug interactions: A review of the mechanisms, in vitro and in silico approaches. Metabolites. 2021; 11(2):75.
Strandell J, Wahlin S. Pharmacodynamic and pharmacokinetic drug interactions reported to VigiBase, the WHO global individual case safety report database. European Journal of Clinical Pharmacology. 2011;67(6):633-41.
Nandi T, Korzekwa K, Nagar S, editors. In-vitro enzyme kinetics of NCD metabolism to DNCD in RLM and RIM. Research Recognition Day; 2022; Temple University School of Pharmacy; 2022.
Nandi T, Korzekwa K, Nagar S, editors. In vitro midazolam metabolism and CYP atypical kinetics in SD rat microsomes. Research Recognition Day; 2021; Temple University School of Pharmacy; 2021.
Zhao M, Ma J, Li M, Zhang Y, Jiang B, Zhao X, et al. Cytochrome P450 enzymes and drug metabolism in humans. International Journal of Molecular Sciences. 2021;22(23):12808.
Hakkola J, Hukkanen J, Turpeinen M, Pelkonen O. Inhibition and induction of CYP enzymes in humans: An update. Archives of Toxicology. 2020;94(11):3671-722.
Lynch T, Neff AP. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. American Family Physician. 2007;76(3): 391-6.
Lin JH. CYP induction-mediated drug interactions: In vitro assessment and clinical implications. Pharmaceutical Research. 2006;23(6):1089-116.
Palatini P, De Martin S. Pharmacokinetic drug interactions in liver disease: An update. World Journal of Gastroenterology. 2016;22(3):1260.
Hewitt N, Lecluyse E, Ferguson S. Induction of hepatic cytochrome P450 enzymes: Methods, mechanisms, recommendations, and in vitro–in vivo correlations. Xenobiotica. 2007;37(10-11):1196-224.
Fuhr U. Induction of Drug metabolising enzymes. Clinical Pharmacokinetics. 2000; 38(6):493-504.
Graham MJ, Lake BG. Induction of drug metabolism: Species differences and toxicological relevance. Toxicology. 2008;254(3):184-91.
Liguori MJ, Lee C-H, Liu H, Ciurlionis R, Ditewig AC, Doktor S, et al. AhR activation underlies the CYP1A autoinduction by A-998679 in rats. Frontiers in Genetics. 2012;3:213.
Pelkonen O, Turpeinen M, Hakkola J, Honkakoski P, Hukkanen J, Raunio H. Inhibition and induction of human cytochrome P450 enzymes: Current status. Archives of Toxicology. 2008;82(10):667-715.
Sinz M, Wallace G, Sahi J. Current industrial practices in assessing CYP450 enzyme induction: Preclinical and clinical. The AAPS Journal. 2008;10(2):391-400.
Hakkola J, Bernasconi C, Coecke S, Richert L, Andersson TB, Pelkonen O. Cytochrome P450 induction and xeno‐sensing receptors pregnane X receptor, constitutive androstane receptor, aryl hydrocarbon receptor and peroxisome proliferator‐activated receptor α at the crossroads of toxicokinetics and toxicodynamics. Basic & Clinical Pharmacology & Toxicology. 2018;123: 42-50.
Muangmoonchai R, Smirlis D, Wong S-C, Edwards M, Phillips IR, Shephard EA. Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor Constitutive Androstane Receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1. Biochemical Journal. 2001;355(1):71-8.
Wyen C, Hendra H, Siccardi M, Platten M, Jaeger H, Harrer T, et al. Cytochrome P450 2B6 (CYP2B6) and Constitutive Androstane Receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens. Journal of Antimicrobial Chemotherapy. 2011;66(9):2092-8.
Yang H, Wang H. Signaling control of the Constitutive Androstane Receptor (CAR). Protein & cell. 2014;5(2):113-23.
Smutny T, Mani S, Pavek P. Post-translational and post-transcriptional modifications of Pregnane X Receptor (PXR) in regulation of the cytochrome P450 superfamily. Current Drug Metabolism. 2013;14(10):1059-69.
Coumoul X, Diry M, Barouki R. PXR-dependent induction of human CYP3A4 gene expression by organochlorine pesticides. Biochemical Pharmacology. 2002;64(10):1513-9.
Wei Y, Tang C, Sant V, Li S, Poloyac SM, Xie W. A molecular aspect in the regulation of drug metabolism: Does PXR-induced enzyme expression always lead to functional changes in drug metabolism? Current Pharmacology Reports. 2016; 2(4):187-92.
Pondugula SR, Dong H, Chen T. Phosphorylation and protein–protein interactions in PXR-mediated CYP3A repression. Expert Opinion on Drug Metabolism & Toxicology. 2009;5(8): 861-73.
Percha B, Altman RB. Informatics confronts drug–drug interactions. Trends in Pharmacological Sciences. 2013;34(3): 178-84.
Zhao L, Au JL-S, Wientjes MG. Comparison of methods for evaluating drug-drug interaction. Frontiers in Bioscience (Elite edition). 2010;2:241.
Hewitt NJ, de Kanter R, LeCluyse E. Induction of Drug metabolizing enzymes: A survey of in vitro methodologies and interpretations used in the pharmaceutical industry—do they comply with FDA recommendations? Chemico-Biological Interactions. 2007;168(1):51-65.
Brandon EF, Raap CD, Meijerman I, Beijnen JH, Schellens JH. An update on in vitro test methods in human hepatic drug biotransformation research: Pros and cons. Toxicology and Applied Pharmacology. 2003;189(3):233-46.
Martignoni M, de Kanter R, Grossi P, Mahnke A, Saturno G, Monshouwer M. An in vivo and in vitro comparison of CYP induction in rat liver and intestine using slices and quantitative RT-PCR. Chemico-Biological Interactions. 2004;151(1):1-11.
Pearen MA, Lim HK, Gratte FD, Fernandez-Rojo MA, Nawaratna SK, Gobert GN, et al. Murine precision-cut liver slices as an ex vivo model of liver biology. JoVE (Journal of Visualized Experiments). 2020(157):e60992.
Bernasconi C, Pelkonen O, Andersson TB, Strickland J, Wilk-Zasadna I, Asturiol D, et al. Validation of in vitro methods for human cytochrome P450 enzyme induction: Outcome of a multi-laboratory study. Toxicology in Vitro. 2019;60:212-28.
Grover GS, Brayman TG, Voorman RL, Ware JA. Development of in vitro methods to predict induction of CYP1A2 and CYP3A4 in humans. Assay and Drug Development Technologies. 2007;5(6): 793-804.
Lu C, Di L. In vitro and in vivo methods to assess pharmacokinetic drug–drug interactions in drug discovery and development. Biopharmaceutics & Drug Disposition. 2020;41(1-2):3-31.
Raucy J, Warfe L, Yueh M-F, Allen SW. A cell-based reporter gene assay for determining induction of CYP3A4 in a high-volume system. Journal of Pharmacology and Experimental Therapeutics. 2002; 303(1):412-23.
Lübberstedt M, Müller-Vieira U, Mayer M, Biemel KM, Knöspel F, Knobeloch D, et al. HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in vitro. Journal of Pharmacological and Toxicological Methods. 2011;63(1):59-68.
Zuo R, Li F, Parikh S, Cao L, Cooper KL, Hong Y, et al. Evaluation of a novel renewable hepatic cell model for prediction of clinical CYP3A4 induction using a correlation-based relative induction score approach. Drug Metabolism and Disposition. 2017;45(2):198-207.
Gomez-Lechon M, Donato M, Lahoz A, Castell J. Cell lines: A tool for in vitro drug metabolism studies. Current Drug Metabolism. 2008;9(1):1-11.
Ripp SL, Mills JB, Fahmi OA, Trevena KA, Liras JL, Maurer TS, et al. Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metabolism and Disposition. 2006; 34(10):1742-8.
Aninat C, Piton A, Glaise D, Le Charpentier T, Langouët S, Morel F, et al. Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells. Drug Metabolism and Disposition. 2006;34(1):75-83.
LeCluyse EL, Alexandre E, Hamilton GA, Viollon-Abadie C, Coon DJ, Jolley S, et al. Isolation and culture of primary human hepatocytes. Basic Cell Culture Protocols: Springer; 2005. p. 207-29.
Bulutoglu B, Rey-Bedón C, Mert S, Tian L, Jang Y-Y, Yarmush ML, et al. A comparison of hepato-cellular in vitro platforms to study CYP3A4 induction. PloS One. 2020;15(2):e0229106.
Luo G, Cunningham M, Kim S, Burn T, Lin J, Sinz M, et al. CYP3A4 induction by drugs: Correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metabolism and Disposition. 2002;30(7): 795-804.
Prueksaritanont T, Chu X, Gibson C, Cui D, Yee KL, Ballard J, et al. drug–drug interaction studies: Regulatory guidance and an industry perspective. The AAPS Journal. 2013;15(3):629-45.
Gowing G, Svendsen S, Svendsen CN. Ex vivo gene therapy for the treatment of neurological disorders. Prog Brain Res. 2017;230:99-132. Epub 20170117.
DOI: 10.1016/bs.pbr.2016.11.003. PubMed PMID: 28552237.
XenoTech. Ex Vivo Enzyme Induction Studies: Xeno Tech; 2022.
Available:https://www.xenotech.com/preclinical-drug-development/in-vitro-studies/enzyme-induction/ex-vivo/
Access on 2022 25 December
Surry DD, Meneses-Lorente G, Heavens R, Jack A, Evans DC. Rapid determination of rat hepatocyte mRNA induction potential using oligonucleotide probes for CYP1A1, 1A2, 3A and 4A1. Xenobiotica. 2000; 30(5):441-56.
DOI: 10.1080/004982500237460. PubMed PMID: 10875679
Baldwin SJ, Bramhall JL, Ashby CA, Yue L, Murdock PR, Hood SR, et al. Cytochrome P450 gene induction in rats ex vivo assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (Taq Man). Drug Metab Dispos. 2006;34(6):1063-9. Epub 20060310.
DOI: 10.1124/dmd.105.008185. PubMed PMID: 16531474.
Gibson UE, Heid CA, Williams PM. A novel method for real time quantitative RT-PCR. Genome Res. 1996;6(10):995-1001.
DOI: 10.1101/gr.6.10.995 PubMed PMID: 8908519.
Godfrey TE, Kelly LA. Development of quantitative reverse transcriptase PCR assays for measuring gene expression. Methods Mol Biol. 2005;291:423-45.
DOI: 10.1385/1-59259-840-4:423 PubMed PMID: 15502240
Bustin SA. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000;25(2):169-93.
DOI: 10.1677/jme.0.0250169 PubMed PMID: 11013345
Ginzinger DG. Gene quantification using real-time quantitative PCR: An emerging technology hits the mainstream. Exp Hematol. 2002;30(6):503-12.
DOI: 10.1016/s0301-472x(02)00806-8 PubMed PMID: 12063017
Gaedigk A, Freeman N, Hartshorne T, Riffel AK, Irwin D, Bishop JR, et al. SNP genotyping using TaqMan technology: The CYP2D6*17 assay conundrum. Sci Rep. 2015;5:9257. Epub 20150319.
DOI: 10.1038/srep09257 PubMed PMID: 25788121; PubMed Central PMCID: PMCPMC4365394
Jin SE, Ha H, Seo CS, Shin HK, Jeong SJ. Expression of cytochrome P450s in the liver of rats administered with socheongryong-tang, a traditional herbal formula. Pharmacogn Mag. 2016; 12(47):211-8.
DOI: 10.4103/0973-1296.186340 PubMed PMID: 27601852; PubMed Central PMCID: PMCPMC4989797
Pan J, Xiang Q, Renwick AB, Price RJ, Ball SE, Kao J, et al. Use of a quantitative real-time reverse transcription-polymerase chain reaction method to study the induction of CYP1A, CYP2B and CYP4A forms in precision-cut rat liver slices. Xenobiotica. 2002;32(9):739-47.
DOI:10.1080/00498250210147115 PubMed PMID: 12396271
Medhurst AD, Harrison DC, Read SJ, Campbell CA, Robbins MJ, Pangalos MN. The use of TaqMan RT-PCR assays for semiquantitative analysis of gene expression in CNS tissues and disease models. J Neurosci Methods. 2000; 98(1):9-20.
DOI: 10.1016/s0165-0270(00)00178-3 PubMed PMID: 10837866
nanoString. nCounter® Analysis Systems Overview: Nano String Technology; 2022.
Available:https://nanostring.com/products/ncounter-analysis-system/ncounter-systems-overview/.
Access on 2022 25 December
Klein K, Thomas M, Winter S, Nussler AK, Niemi M, Schwab M, et al. PPARA: A novel genetic determinant of CYP3A4 In vitro and In vivo. Clinical Pharmacology & Therapeutics. 2012;91(6):1044-52.
Palamanda JR, Kumari P, Murgolo N, Benbow L, Lin X, Nomeir AA. Evaluation of CYP1A1 and CYP2B1/2 m-RNA induction in rat liver slices using the Nano String technology: A novel tool for drug discovery lead optimization. Drug Metab Lett. 2009;3(3):171-5. Epub 20090801.
DOI: 10.2174/187231209789352094 PubMed PMID: 19702544
Martignoni M, De Kanter R, Grossi P, Saturno G, Barbaria E, Monshouwer M. An In vivo and In vitro comparison of CYP gene induction in mice using liver slices and quantitative RT-PCR. Toxicology in vitro. 2006;20(1):125-31.
Martignoni M, Groothuis GM, de Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opinion on Drug Metabolism & Toxicology. 2006;2(6):875-94.
Ohno Y, Hisaka A, Ueno M, Suzuki H. General framework for the prediction of oral drug interactions caused by CYP3A4 induction from In vivo information. Clinical Pharmacokinetics. 2008;47(10): 669-80.
Pelkonen O. Human CYPs: In vivo and clinical aspects. Drug Metabolism Reviews. 2002;34(1-2):37-46.
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