Skip to main content

In Vivo Models for Evaluation of Drug Efficacy: Demand and Challenges

  • Chapter
  • First Online:
Drugs and a Methodological Compendium

Abstract

Drug screening for a disease may take more than 5 to 7 years and typically involves scanning of a number of molecules, acting as potential drug candidates. These drugs are tested for pharmacological as well as toxicological evaluations to uncover their therapeutic applications for a particular disease. These tests followed by clinical trials allow studying the safety, efficacy and pharmacology of that molecule. These tests are conducted on a wide range of in vitro and in vivo model systems. Though in vitro investigations are cost-effective and reduce experimental restrictions, these studies do not closely mimic the live scenario of the biological system. Therefore, in vivo testing is still mandated to comprehensively characterise the therapeutic behaviour of the drug. Further, to assess the human risk upon exposure to the drug, in vitro toxicodynamic results are associated with in vivo toxicokinetics using complex mathematical models. Despite significant breakthroughs in the field of in vitro test systems including 3D cell and organ culture techniques, the translational value of these systems is limited, and still mankind needs to traverse a long road ahead in this field. Undoubtedly, the information provided by in vivo models reflects a closer approximation to humans with respect to drug permeability, distribution, metabolism as well as excretion. In view of these facts, this chapter describes several contemporary animal models representing diverse diseases, employed for testing the efficacy of a drug.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Adamson PB, Vanoli E (2001) Early autonomic and repolarization abnormalities contribute to lethal arrhythmias in chronic ischemic heart failure: characteristics of a novel heart failure model in dogs with postmyocardial infarction left ventricular dysfunction. J Am Coll Cardiol 37:1741–1748

    Article  CAS  PubMed  Google Scholar 

  • Agotegaray M, Gumilar F, Boeris M, Toso R, Minetti A (2014) Enhanced analgesic properties and reduced ulcerogenic effect of a mononuclear copper (II) complex with fenoprofen in comparison to the parent drug: promising insights in the treatment of chronic inflammatory diseases. BioMed Res Int 2014:505987

    Article  PubMed  PubMed Central  Google Scholar 

  • Alarcon RT, da Rocha Corrêa Fernandes A, Laurindo IM, Bértolo MB, Pinheiro GC, Andrade LE (2015) Characterization of cumulative joint damage patterns in patients with rheumatoid arthritis: a clinical, serological, and gene polymorphism perspective. J Rheumatol 42:405–412

    Article  PubMed  Google Scholar 

  • Ali MS, Tiscareno-Grejada I, Locovei S, Smiley R, Collins T, Sarosiek J, McCallum R (2012) Gender and estradiol as major factors in the expression and dimerization of nNOSα in rats with experimental diabetic gastroparesis. Dig Dis Sci 57:2814–2825

    Article  Google Scholar 

  • Ali Y, Alam MS, Hamid H, Husain A, Kharbanda C, Bano S, Nazreen S, Haider S (2014) Attenuation of inflammatory mediators, oxidative stress and toxic risk evaluation of Aporosa lindleyana Baill bark extract. J Ethnopharmacol 155:1513–1521

    Article  CAS  PubMed  Google Scholar 

  • Americo JL, Sood CL, Cotter CA, Vogel JL, Kristie TM, Moss B, Earl PL (2014) Susceptibility of the wild-derived inbred CAST/Ei mouse to infection by orthopoxviruses analyzed by live bioluminescence imaging. Virology 449:120–132

    Article  CAS  PubMed  Google Scholar 

  • Anders H-J, Vielhauer V (2007) Identifying and validating novel targets with in vivo disease models: guidelines for study design. Drug Discov Today 12:446–451

    Article  CAS  PubMed  Google Scholar 

  • Andrade E, Bento A, Cavalli J, Oliveira S, Schwanke R, Siqueira J, Freitas C, Marcon R, Calixto J (2016) Non-clinical studies in the process of new drug development-part II: good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies. Braz J Med Biol Res 49:e5646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andreu N, Zelmer A, Sampson SL, Ikeh M, Bancroft GJ, Schaible UE, Wiles S, Robertson BD (2013) Rapid in vivo assessment of drug efficacy against Mycobacterium tuberculosis using an improved firefly luciferase. J Antimicrob Chemother 68:2118–2127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Annahazi A, Dabek M, Gecse K, Salvador-Cartier C, Polizzi A, Rosztoczy A, Roka R, Theodorou V, Wittmann T, Bueno L (2012) Proteinase-activated receptor-4 evoked colorectal analgesia in mice: an endogenously activated feed-back loop in visceral inflammatory pain. Neurogastroenterol Motil 24:76–e13

    Article  CAS  PubMed  Google Scholar 

  • Asano T, Aida S, Suemasu S, Mizushima T (2016) Anethole restores delayed gastric emptying and impaired gastric accommodation in rodents. Biochem Biophys Res Commun 472:125–130

    Article  CAS  PubMed  Google Scholar 

  • Ashe KH, Zahs KR (2010) Probing the biology of Alzheimer’s disease in mice. Neuron 66:631–645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asquith DL, Miller AM, McInnes IB, Liew FY (2009) Animal models of rheumatoid arthritis. Eur J Immunol 39:2040–2044

    Article  CAS  PubMed  Google Scholar 

  • Badimon L (2001) Atherosclerosis and thrombosis: lessons from animal models. Thromb Haemost 86:356–365

    Article  CAS  PubMed  Google Scholar 

  • Balogun SO, Damazo AS, de Oliveira Martins DT (2015) Helicteres sacarolha A. St.-Hil. et al.: gastroprotective and possible mechanism of actions in experimental animals. J Ethnopharmacol 166:176–184

    Article  PubMed  Google Scholar 

  • Balouiri M, Sadiki M, Ibnsouda SK (2016) Methods for in vitro evaluating antimicrobial activity: a review. J Pharm Anal 6:71–79

    Article  PubMed  Google Scholar 

  • Bao L, Deng W, Huang B, Gao H, Liu J, Ren L, Wei Q, Yu P, Xu Y, Qi F (2020) The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature 583:830–833

    Article  CAS  PubMed  Google Scholar 

  • Barretti D, Melo S, Oliveira E, Barauna V (2017) Resistance training attenuates salt overload-induced cardiac remodeling and diastolic dysfunction in normotensive rats. Braz J Med Biol Res 50

    Google Scholar 

  • Barry AL (1999) Methods for determining bactericidal activity of antimicrobial agents: approved guidelines. National committee for clinical laboratory standards, Wayne, PA

    Google Scholar 

  • Batista LM, Lima GRDM, De Almeida ABA, Magri LDP, Calvo TR, Ferreira AL, Pellizzon CH, Hiruma-Lima CA, Vilegas W, Sano PT (2015) Ulcer healing and mechanism (s) of action involved in the gastroprotective activity of fractions obtained from Syngonanthus arthrotrichus and Syngonanthus bisulcatus. BMC Complement Altern Med 15:1–9

    Article  CAS  Google Scholar 

  • Belevych AE, Terentyev D, Terentyeva R, Nishijima Y, Sridhar A, Hamlin RL, Carnes CA, Györke S (2011) The relationship between arrhythmogenesis and impaired contractility in heart failure: role of altered ryanodine receptor function. Cardiovasc Res 90:493–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bibby M (1999) Making the most of rodent tumour systems in cancer drug discovery. Br J Cancer 79:1633–1640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Björklund LM, Sánchez-Pernaute R, Chung S, Andersson T, Chen IYC, McNaught KSP, Brownell A-L, Jenkins BG, Wahlestedt C, Kim K-S (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci 99:2344–2349

    Article  PubMed  PubMed Central  Google Scholar 

  • van den Bos EJ, Mees BM, de Waard MC, de Crom R, Duncker DJ (2005) A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation. Am J Phys Heart Circ Phys 289:H1291–H1300

    Google Scholar 

  • Brake K, Gumireddy A, Tiwari A, Chauhan H, Kumari D (2017) In vivo studies for drug development via oral delivery: challenges, animal models and techniques. Pharm Anal Acta 8:560. https://doi.org/10.4172/2153-2435.1000560

    Article  CAS  Google Scholar 

  • Bullard TA, Protack TL, Aguilar F, Bagwe S, Massey HT, Blaxall BC (2008) Identification of Nogo as a novel indicator of heart failure. Physiol Genomics 32:182–189

    Article  CAS  PubMed  Google Scholar 

  • Bushra R, Aslam N, Khan AY (2011) Food-drug interactions. Oman Med J 26:77

    Article  PubMed  PubMed Central  Google Scholar 

  • Camacho P, Fan H, Liu Z, He J-Q (2016) Small mammalian animal models of heart disease. Am J Cardiovasc Dis 6:70

    CAS  PubMed  PubMed Central  Google Scholar 

  • Campbell IK, Hamilton JA, Wicks IP (2000) Collagen-induced arthritis in C57BL/6 (H-2b) mice: new insights into an important disease model of rheumatoid arthritis. Eur J Immunol 30:1568–1575

    Article  CAS  PubMed  Google Scholar 

  • Cardot J, Beyssac E, Alric M (2007) In vitro-in vivo correlation: importance of dissolution in IVIVC. Dissolut Technol 14:15

    Article  CAS  Google Scholar 

  • Carmona S, Hardy J, Guerreiro R (2018) The genetic landscape of Alzheimer disease. Handb Clin Neurol 148:395–408

    Article  PubMed  Google Scholar 

  • Chang X, Luo F, Jiang W, Zhu L, Gao J, He H, Wei T, Gong S, Yan T (2015) Protective activity of salidroside against ethanol-induced gastric ulcer via the MAPK/NF-κB pathway in vivo and in vitro. Int Immunopharmacol 28:604–615

    Article  CAS  PubMed  Google Scholar 

  • Chen X-Y, Chen H-M, Liu Y-H, Zhang Z-B, Zheng Y-F, Su Z-Q, Zhang X, Xie J-H, Liang Y-Z, Fu L-D (2016) The gastroprotective effect of pogostone from Pogostemonis Herba against indomethacin-induced gastric ulcer in rats. Exp Biol Med 241:193–204

    Article  CAS  Google Scholar 

  • Choma IM, Grzelak EM (2011) Bioautography detection in thin-layer chromatography. J Chromatogr A 1218:2684–2691

    Article  CAS  PubMed  Google Scholar 

  • Chow PK, Ng RT, Ogden BE (2008) Using animal models in biomedical research: a primer for the investigator. World Scientific

    Book  Google Scholar 

  • Corbett T, Polin L, LoRusso P, Valeriote F, Panchapor C, Pugh S, White K, Knight J, Demchik L, Jones J (2004) In vivo methods for screening and preclinical testing. In: Anticancer drug development guide. Springer, pp 99–123

    Chapter  Google Scholar 

  • Cosyns S, Dhaese I, Thoonen R, Buys E, Vral A, Brouckaert P, Lefebvre R (2013) Heme deficiency of soluble guanylate cyclase induces gastroparesis. Neurogastroenterol Motil 25:e339–e352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Courtenay J, Dallman MJ, Dayan A, Martin A, Mosedale B (1980) Immunisation against heterologous type II collagen induces arthritis in mice. Nature 283:666–668

    Article  CAS  PubMed  Google Scholar 

  • Creed RB, Goldberg MS (2018) New developments in genetic rat models of Parkinson’s disease. Mov Disord 33:717–729

    Article  PubMed  PubMed Central  Google Scholar 

  • Creedon CT, Verhulst P-J, Choi KM, Mason JE, Linden DR, Szurszewski JH, Gibbons SJ, Farrugia G (2013) Assessment of gastric emptying in non-obese diabetic mice using a [13C]-octanoic acid breath test. J Vis Exp 73:e50301. https://doi.org/10.3791/50301

    Article  Google Scholar 

  • Dai F, Lei Y, Li S, Song G, Chen JD (2013a) Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats. Am J Physiol Gastrointest Liver Physiol 305:G333–G339

    Article  CAS  PubMed  Google Scholar 

  • Dai T, Gupta A, Huang Y-Y, Yin R, Murray CK, Vrahas MS, Sherwood ME, Tegos GP, Hamblin MR (2013b) Blue light rescues mice from potentially fatal Pseudomonas aeruginosa burn infection: efficacy, safety, and mechanism of action. Antimicrob Agents Chemother 57:1238–1245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai T, Kharkwal GB, Zhao J, Denis TGS, Wu Q, Xia Y, Huang L, Sharma SK, d’Enfert C, Hamblin MR (2011) Ultraviolet-C light for treatment of Candida albicans burn infection in mice. Photochem Photobiol 87:342–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davidson M, Lindsey J, Davis J (1987) Requirements and selection of an animal model. Isr J Med Sci 23:551–555

    CAS  PubMed  Google Scholar 

  • Dawson TM, Golde TE, Lagier-Tourenne C (2018) Animal models of neurodegenerative diseases. Nat Neurosci 21:1370–1379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dayan V, Yannarelli G, Filomeno P, Keating A (2012) Human mesenchymal stromal cells improve scar thickness without enhancing cardiac function in a chronic ischaemic heart failure model. Interact Cardiovasc Thorac Surg 14:516–520

    Article  PubMed  PubMed Central  Google Scholar 

  • Dinnon KH, Leist SR, Schäfer A, Edwards CE, Martinez DR, Montgomery SA, West A, Yount BL, Hou YJ, Adams LE (2020) A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures. Nature 586:560–566

    Article  PubMed  PubMed Central  Google Scholar 

  • Dressman J, Vertzoni M, Goumas K, Reppas C (2007) Estimating drug solubility in the gastrointestinal tract. Adv Drug Deliv Rev 59:591–602

    Article  CAS  PubMed  Google Scholar 

  • Ducharme J, Dudley A, Thompson R (2006) Pharmacokinetic issue in drug discovery. In: Drug discovery and development. Churchill Livingstone Elsevier, Philadelphia, pp 141–161

    Google Scholar 

  • Duris FH, Fava RA, Noelle RJ (1994) Collagen-induced arthritis as a model of rheumatoid arthritis. Clin Immunol Immunopathol 73:11–18

    Article  Google Scholar 

  • Dykes DJ, Waud WR (2002) Murine L1210 and P388 leukemias. In: Tumor models in cancer research. Humana Press, Totowa, pp 23–40

    Google Scholar 

  • Enjalbert B, Rachini A, Vediyappan G, Pietrella D, Spaccapelo R, Vecchiarelli A, Brown AJ, d'Enfert C (2009) A multifunctional, synthetic Gaussia princeps luciferase reporter for live imaging of Candida albicans infections. Infect Immun 77:4847–4858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan J, Kitajima S, Watanabe T, Xu J, Zhang J, Liu E, Chen YE (2015) Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine. Pharmacol Ther 146:104–119

    Article  CAS  PubMed  Google Scholar 

  • Fatma G, Mouna BF, Mondher M, Ahmed L (2014) In-vitro assessment of antioxidant and antimicrobial activities of methanol extracts and essential oil of Thymus hirtus sp. algeriensis. Lipids Health Dis 13:1–12

    Article  Google Scholar 

  • Favre-Godal Q, Queiroz EF, Wolfender J-L (2013) Latest developments in assessing antifungal activity using TLC-bioautography: a review. J AOAC Int 96:1175–1188

    Article  CAS  PubMed  Google Scholar 

  • Food and Drug Administration, CDER, CBER, US Department of Human Health Services (2019) M4E(R2): the CTD—efficacy guidance for industry, Revision 1. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf

  • Franke-Fayard B, Waters AP, Janse CJ (2006) Real-time in vivo imaging of transgenic bioluminescent blood stages of rodent malaria parasites in mice. Nat Protoc 1:476–485

    Article  CAS  PubMed  Google Scholar 

  • Freedman LP, Venugopalan G, Wisman R (2017) Reproducibility2020: progress and priorities. F1000Research 6:604

    Article  PubMed  PubMed Central  Google Scholar 

  • Galandrin S, Oligny-Longpré G, Bouvier M (2007) The evasive nature of drug efficacy: implications for drug discovery. Trends Pharmacol Sci 28:423–430

    Article  CAS  PubMed  Google Scholar 

  • Geran RI, Greenberg NH, MacDonald MM, Schumacher AM (1972) Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother Rep 3:1–103

    Google Scholar 

  • Ghoneim HE, McCullers JA (2014) Adjunctive corticosteroid therapy improves lung immunopathology and survival during severe secondary pneumococcal pneumonia in mice. J Infect Dis 209:1459–1468

    Article  CAS  PubMed  Google Scholar 

  • Golberg A, Broelsch GF, Vecchio D, Khan S, Hamblin MR, Austen WG Jr, Sheridan RL, Yarmush ML (2014) Eradication of multidrug-resistant A. baumannii in burn wounds by antiseptic pulsed electric field. Technology 2:153–160

    Article  PubMed  PubMed Central  Google Scholar 

  • Golde TE, Schneider LS, Koo EH (2011) Anti-Aβ therapeutics in Alzheimer’s disease: the need for a paradigm shift. Neuron 69:203–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • González-Rosa JM, Burns CE, Burns CG (2017) Zebrafish heart regeneration: 15 years of discoveries. Regeneration 4:105–123

    Article  PubMed  PubMed Central  Google Scholar 

  • Gralinski LE, Menachery VD (2020) Return of the coronavirus: 2019-nCoV. Viruses 12:135

    Article  PubMed  PubMed Central  Google Scholar 

  • Gralinski M, Neves LA, Tiniakova O (2020) Methods to induce cardiac hypertrophy and insufficiency. In: Drug discovery and evaluation: pharmacological assays. Springer, Berlin, p 287

    Google Scholar 

  • Grisel P, Meinhardt A, Lehr H-A, Kappenberger L, Barrandon Y, Vassalli G (2008) The MRL mouse repairs both cryogenic and ischemic myocardial infarcts with scar. Cardiovasc Pathol 17:14–22

    Article  CAS  PubMed  Google Scholar 

  • Gu H, Chen Q, Yang G, He L, Fan H, Deng Y-Q, Wang Y, Teng Y, Zhao Z, Cui Y (2020a) Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science 369:1603–1607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu H, Chen Q, Yang G, He L, Fan H, Deng Y-Q, Wang Y, Teng Y, Zhao Z, Cui Y (2020b) Rapid adaptation of SARS-CoV-2 in BALB/c mice: novel mouse model for vaccine efficacy. BioRxiv. https://doi.org/10.1101/2020.05.02.073411

  • Haass C, De Strooper B (1999) The presenilins in Alzheimer’s disease—proteolysis holds the key. Science 286:916–919

    Article  CAS  PubMed  Google Scholar 

  • Hamblin MR, Hasan T (2004) Photodynamic therapy: a new antimicrobial approach to infectious disease? Photochem Photobiol Sci 3:436–450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamblin MR, Zahra T, Contag CH, McManus AT, Hasan T (2003) Optical monitoring and treatment of potentially lethal wound infections in vivo. J Infect Dis 187:1717–1726

    Article  PubMed  Google Scholar 

  • Hamburger MO, Cordell GA (1987) A direct bioautographic TLC assay for compounds possessing antibacterial activity. J Nat Prod 50:19–22

    Article  CAS  PubMed  Google Scholar 

  • Hardy J, Chu P, Contag CH (2009) Foci of Listeria monocytogenes persist in the bone marrow. Dis Model Mech 2:39–46

    Article  PubMed  Google Scholar 

  • Hassan AO, Case JB, Winkler ES, Thackray LB, Kafai NM, Bailey AL, McCune BT, Fox JM, Chen RE, Alsoussi WB (2020) A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies. Cell 182:744–753.e4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haubner BJ, Adamowicz-Brice M, Khadayate S, Tiefenthaler V, Metzler B, Aitman T, Penninger JM (2012) Complete cardiac regeneration in a mouse model of myocardial infarction. Aging (Albany NY) 4:966

    Article  CAS  PubMed  Google Scholar 

  • Hearse DJ, Sutherland FJ (2000) Experimental models for the study of cardiovascular function and disease. Pharmacol Res 41:597–603

    Article  CAS  PubMed  Google Scholar 

  • Henriques C, Castro DP, Gomes LH, Garcia ES, de Souza W (2012) Bioluminescent imaging of Trypanosoma cruzi infection in Rhodnius prolixus. Parasit Vectors 5:1–15

    Article  Google Scholar 

  • Holtzman DM, Carrillo MC, Hendrix JA, Bain LJ, Catafau AM, Gault LM, Goedert M, Mandelkow E, Mandelkow E-M, Miller DS (2016) Tau: from research to clinical development. Alzheimers Dement 12:1033–1039

    Article  PubMed  Google Scholar 

  • Hosoya T, Matsumoto K, Tashima K, Nakamura H, Fujino H, Murayama T, Horie S (2014) TRPM 8 has a key role in experimental colitis-induced visceral hyperalgesia in mice. Neurogastroenterol Motil 26:1112–1121

    Article  CAS  PubMed  Google Scholar 

  • Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395:497–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang L, Wang M, Dai T, Sperandio FF, Huang Y-Y, Xuan Y, Chiang LY, Hamblin MR (2014) Antimicrobial photodynamic therapy with decacationic monoadducts and bisadducts of [70] fullerene: in vitro and in vivo studies. Nanomedicine 9:253–266

    Article  CAS  PubMed  Google Scholar 

  • Hughes JP, Rees S, Kalindjian SB, Philpott KL (2011) Principles of early drug discovery. Br J Pharmacol 162:1239–1249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaarin K, Mustafa MR, Leong X-F (2011) The effects of heated vegetable oils on blood pressure in rats. Clinics 66:2125–2132

    Article  PubMed  PubMed Central  Google Scholar 

  • Jankovic J, Tan EK (2020) Parkinson’s disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry 91:795–808

    Article  PubMed  Google Scholar 

  • Jiang R-D, Liu M-Q, Chen Y, Shan C, Zhou Y-W, Shen X-R, Li Q, Zhang L, Zhu Y, Si H-R (2020) Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2. Cell 182:50–58.e8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • EU Joint Programme – Neurodegenerative Disease Research (JPND) (2014) Experimental models for neurodegenerative diseases. JNPD Research: EU Joint programme – Neurodegenerative disease research, pp 5–42. http://www.extranet-jpnd.eu

  • Johnson AC, Greenwood-Van Meerveld B (2017) Critical evaluation of animal models of gastrointestinal disorders. Handb Exp Pharmacol 239:289–317

    Article  CAS  PubMed  Google Scholar 

  • Júnior FE, de Oliveira DR, Boligon AA, Athayde ML, Kamdem JP, Macedo GE, da Silva GF, de Menezes IR, Costa JG, Coutinho HDM (2014) Protective effects of Croton campestris A. St-Hill in different ulcer models in rodents: evidence for the involvement of nitric oxide and prostaglandins. J Ethnopharmacol 153:469–477

    Article  PubMed  Google Scholar 

  • Kannan K, Ortmann RA, Kimpel D (2005) Animal models of rheumatoid arthritis and their relevance to human disease. Pathophysiology 12:167–181

    Article  PubMed  Google Scholar 

  • Kari G, Rodeck U, Dicker AP (2007) Zebrafish: an emerging model system for human disease and drug discovery. Clin Pharmacol Ther 82:70–80

    Article  CAS  PubMed  Google Scholar 

  • Karlsson EA, Meliopoulos VA, Savage C, Livingston B, Mehle A, Schultz-Cherry S (2015) Visualizing real-time influenza virus infection, transmission and protection in ferrets. Nat Commun 6:1–10

    Article  Google Scholar 

  • Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D, Kollias G (1991) Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 10:4025–4031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim EY, Moudgil KD (2009) The determinants of susceptibility/resistance to adjuvant arthritis in rats. Arthritis Res Ther 11:1–9

    Article  Google Scholar 

  • Kim J, Chakrabarty P, Hanna A, March A, Dickson DW, Borchelt DR, Golde T, Janus C (2013) Normal cognition in transgenic BRI2-Aβ mice. Mol Neurodegener 8:1–12

    Article  CAS  Google Scholar 

  • Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK (2020) Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe 27:704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kimura Y, Sumiyoshi M (2012) Effects of an Atractylodes lancea rhizome extract and a volatile component β-eudesmol on gastrointestinal motility in mice. J Ethnopharmacol 141:530–536

    Article  CAS  PubMed  Google Scholar 

  • Kinoshita J, Clark T (2007) Alzforum. Methods Mol Biol 401:365–381

    Article  PubMed  Google Scholar 

  • Klepser ME, Ernst EJ, Lewis RE, Ernst ME, Pfaller MA (1998) Influence of test conditions on antifungal time-kill curve results: proposal for standardized methods. Antimicrob Agents Chemother 42:1207–1212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kruczynski A, Colpaert F, Tarayre J-P, Mouillard P, Fahy J, Hill BT (1998) Preclinical in vivo antitumor activity of vinflunine, a novel fluorinated Vinca alkaloid. Cancer Chemother Pharmacol 41:437–447

    Article  CAS  PubMed  Google Scholar 

  • Kudryavtsev KV, Markevich AO, Virchenko OV, Falalyeyeva TM, Beregova TV, Ostapchenko LI, Zabolotnev DV, Zefirov NS (2014) Pharmacological correction of stress-induced gastric ulceration by novel small-molecule agents with antioxidant profile. ScientificWorldJournal 2014:217039

    Article  PubMed  PubMed Central  Google Scholar 

  • LaFerla FM, Green KN (2012) Animal models of Alzheimer disease. Cold Spring Harb Perspect Med 2:a006320

    Article  PubMed  PubMed Central  Google Scholar 

  • Lai AC, Wallner K, Cao JM, Chen LS, Karagueuzian HS, Fishbein MC, Chen PS, Sharifi BG (2000) Colocalization of tenascin and sympathetic nerves in a canine model of nerve sprouting and sudden cardiac death. J Cardiovasc Electrophysiol 11:1345–1351

    Article  CAS  PubMed  Google Scholar 

  • Lambrechts SA, Demidova TN, Aalders MC, Hasan T, Hamblin MR (2005) Photodynamic therapy for Staphylococcus aureus infected burn wounds in mice. Photochem Photobiol Sci 4:503–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lanao J, Fraile M (2005) Drug tissue distribution: study methods and therapeutic implications. Curr Pharm Des 11:3829–3845

    Article  CAS  PubMed  Google Scholar 

  • Langdon S, Hendriks H, Braakhuis B-J, Pratesi G, Berger D, Fodstad Ø, Fiebig H, Boven E (1994) Preclinical phase II studies in human tumor xenografts: a European multicenter follow-up study. Ann Oncol 5:415–422

    Article  CAS  PubMed  Google Scholar 

  • de Lange WJ, Grimes AC, Hegge LF, Ralphe JC (2013) Ablation of cardiac myosin–binding protein-C accelerates contractile kinetics in engineered cardiac tissue. J Gen Physiol 141:73–84

    Article  PubMed  PubMed Central  Google Scholar 

  • Larcher T, Lafoux A, Tesson L, Remy S, Thepenier V, François V, Le Guiner C, Goubin H, Dutilleul M, Guigand L (2014) Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy. PLoS One 9:e110371

    Article  PubMed  PubMed Central  Google Scholar 

  • Leong XF, Aishah A, Aini UN, Das S, Jaarin K (2008) Heated palm oil causes rise in blood pressure and cardiac changes in heart muscle in experimental rats. Arch Med Res 39:567–572

    Article  CAS  PubMed  Google Scholar 

  • Li P, Schwarz EM (2003) The TNF-α transgenic mouse model of inflammatory arthritis. Springer Semin Immunopathol 25:19–33

    Article  PubMed  Google Scholar 

  • Li S, Chen J (2014) Decreased L-type calcium current in antral smooth muscle cells of STZ-induced diabetic rats. Neurogastroenterol Motil 26:971–979

    Article  CAS  PubMed  Google Scholar 

  • Li W-R, Shi Q-S, Dai H-Q, Liang Q, Xie X-B, Huang X-M, Zhao G-Z, Zhang L-X (2016) Antifungal activity, kinetics and molecular mechanism of action of garlic oil against Candida albicans. Sci Rep 6:1–9

    Google Scholar 

  • Liao J, Huang W, Liu G (2017) Animal models of coronary heart disease. J Biomed Res 31:3

    Article  CAS  Google Scholar 

  • Lieschke GJ, Currie PD (2007) Animal models of human disease: zebrafish swim into view. Nat Rev Genet 8:353–367

    Article  CAS  PubMed  Google Scholar 

  • Lin Y, Roman K, Foust K, Kaspar B, Bailey M, Stephens R (2011) Glutamate transporter GLT-1 upregulation attenuates visceral nociception and hyperalgesia via spinal mechanisms not related to anti-inflammatory or probiotic effects. Pain Res Treat 2011:507029

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lindsey ML, Bolli R, Canty JM, Du X-J, Frangogiannis NG, Frantz S, Gourdie RG, Holmes JW, Jones SP, Kloner RA et al (2018) Guidelines for experimental models of myocardial ischemia and infarction. Am J Physiol Heart Circ Physiol 314:H812–H838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lipsky MS, Sharp LK (2001) From idea to market: the drug approval process. J Am Board Fam Pract 14:362–367

    CAS  PubMed  Google Scholar 

  • Liu C, Oikonomopoulos A, Sayed N, Wu JC (2018) Modeling human diseases with induced pluripotent stem cells: from 2D to 3D and beyond. Development 145:dev156166

    Article  PubMed  PubMed Central  Google Scholar 

  • Lu H, Xu X, Zhang M, Cao R, Bråkenhielm E, Li C, Lin H, Yao G, Sun H, Qi L (2007) Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs. Proc Natl Acad Sci 104:12140–12145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu S, Zhao Y, Yu W, Yang Y, Gao J, Wang J, Kuang D, Yang M, Yang J, Ma C (2020a) Comparison of nonhuman primates identified the suitable model for COVID-19. Signal Transduct Target Ther 5:1–9

    Google Scholar 

  • Lu S, Zhao Y, Yu W, Yang Y, Gao J, Wang J, Kuang D, Yang M, Yang J, Ma C (2020b) Comparison of SARS-CoV-2 infections among 3 species of non-human primates. BioRxiv:1–27. https://doi.org/10.1101/2020.04.08.031807

  • Lum-Naihe K, Toedebusch R, Mahmood A, Bajwa J, Carmack T, Kumar SA, Ardhanari S, DeMarco VG, Emter CA, Pulakat L (2017) Cardiovascular disease progression in female Zucker Diabetic Fatty rats occurs via unique mechanisms compared to males. Sci Rep 7:1–16

    Article  CAS  Google Scholar 

  • Magaldi S, Mata-Essayag S, De Capriles CH, Pérez C, Colella M, Olaizola C, Ontiveros Y (2004) Well diffusion for antifungal susceptibility testing. Int J Infect Dis 8:39–45

    Article  CAS  PubMed  Google Scholar 

  • Martini L, Fini M, Giavaresi G, Giardino R (2001) Sheep model in orthopedic research: a literature review. Comp Med 51:292–299

    CAS  PubMed  Google Scholar 

  • McGonigle P, Ruggeri B (2014) Animal models of human disease: challenges in enabling translation. Biochem Pharmacol 87:162–171

    Article  CAS  PubMed  Google Scholar 

  • McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P (2005) Aβ42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47:191–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Milani-Nejad N, Janssen PM (2014) Small and large animal models in cardiac contraction research: advantages and disadvantages. Pharmacol Ther 141:235–249

    Article  CAS  PubMed  Google Scholar 

  • Ministry of Environment and Forests, Govt. of India (2007) Guidelines on the regulation of scientific experiments on animals, pp 1–144

    Google Scholar 

  • Montgomery M, Ahadian S, Huyer LD, Rito ML, Civitarese RA, Vanderlaan RD, Wu J, Reis LA, Momen A, Akbari S (2017) Flexible shape-memory scaffold for minimally invasive delivery of functional tissues. Nat Mater 16:1038–1046

    Article  CAS  PubMed  Google Scholar 

  • Mook-Kanamori BB, Rouse MS, Kang C-I, van de Beek D, Steckelberg JM, Patel R (2009) Daptomycin in experimental murine pneumococcal meningitis. BMC Infect Dis 9:1–9

    Article  Google Scholar 

  • Mosci P, Pericolini E, Gabrielli E, Kenno S, Perito S, Bistoni F, d’Enfert C, Vecchiarelli A (2013) A novel bioluminescence mouse model for monitoring oropharyngeal candidiasis in mice. Virulence 4:250–254

    Article  PubMed  PubMed Central  Google Scholar 

  • Mukherjee R, Brinsa TA, Dowdy KB, Scott AA, Baskin JM, Deschamps AM, Lowry AS, Escobar GP, Lucas DG, Yarbrough WM (2003) Myocardial infarct expansion and matrix metalloproteinase inhibition. Circulation 107:618–625

    Article  CAS  PubMed  Google Scholar 

  • Munder A, Wölbeling F, Klockgether J, Wiehlmann L, Tümmler B (2014) In vivo imaging of bioluminescent Pseudomonas aeruginosa in an acute murine airway infection model. Pathog Dis 72:74–77

    Article  CAS  PubMed  Google Scholar 

  • Nordin N, Salama SM, Golbabapour S, Hajrezaie M, Hassandarvish P, Kamalidehghan B, Majid NA, Hashim NM, Omar H, Fadaienasab M (2014) Anti-ulcerogenic effect of methanolic extracts from Enicosanthellum pulchrum (King) Heusden against ethanol-induced acute gastric lesion in animal models. PLoS One 9:e111925

    Article  PubMed  PubMed Central  Google Scholar 

  • Nunes S, Rolo AP, Palmeira CM, Reis F (2017) Diabetic cardiomyopathy: focus on oxidative stress, mitochondrial dysfunction and inflammation. In: Cardiomyopathies—types and treatments. Intech, pp 235–257

    Google Scholar 

  • Olson EN (2006) Gene regulatory networks in the evolution and development of the heart. Science 313:1922–1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ozcan C, Battaglia E, Young R, Suzuki G (2015) LKB1 knockout mouse develops spontaneous atrial fibrillation and provides mechanistic insights into human disease process. J Am Heart Assoc 4:e001733

    Article  PubMed  PubMed Central  Google Scholar 

  • Palleria C, Di Paolo A, Giofrè C, Caglioti C, Leuzzi G, Siniscalchi A, De Sarro G, Gallelli L (2013) Pharmacokinetic drug-drug interaction and their implication in clinical management. J Res Med Sci 18:601

    PubMed  PubMed Central  Google Scholar 

  • Pandey S, Pandey P, Tiwari G, Tiwari R (2010) Bioanalysis in drug discovery and development. Pharm Methods 1:14–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park S-J, Yu K-M, Kim Y-I, Kim S-M, Kim E-H, Kim S-G, Kim EJ, Casel MAB, Rollon R, Jang S-G (2020) Antiviral efficacies of FDA-approved drugs against SARS-CoV-2 infection in ferrets. MBio 11:e01114–e01120

    Article  PubMed  PubMed Central  Google Scholar 

  • Porrello ER, Mahmoud AI, Simpson E, Johnson BA, Grinsfelder D, Canseco D, Mammen PP, Rothermel BA, Olson EN, Sadek HA (2013) Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc Natl Acad Sci 110:187–192

    Article  CAS  PubMed  Google Scholar 

  • Price DL, Tanzi RE, Borchelt DR, Sisodia SS (1998) Alzheimer's disease: genetic studies and transgenic models. Annu Rev Genet 32:461–493

    Article  CAS  PubMed  Google Scholar 

  • Probert L, Akassoglou K, Alexopoulou L, Douni E, Haralambous S, Hill S, Kassiotis G, Kontoyiannis D, Pasparakis M, Plows D (1996) Dissection of the pathologies induced by transmembrane and wild-type tumor necrosis factor in transgenic mice. J Leukoc Biol 59:518–525

    Article  CAS  PubMed  Google Scholar 

  • Rathore A, Rahman MU, Siddiqui AA, Ali A, Shaharyar M (2014) Design and synthesis of benzimidazole analogs endowed with oxadiazole as selective COX-2 inhibitor. Arch Pharm 347:923–935

    Article  CAS  Google Scholar 

  • Ravella K, Al-Hendy A, Sharan C, Hale A, Channon K, Srinivasan S, Gangula P (2013) Chronic estrogen deficiency causes gastroparesis by altering neuronal nitric oxide synthase function. Dig Dis Sci 58:1507–1515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reichardt SD, Weinhage T, Rotte A, Foeller M, Oppermann M, Lühder F, Tuckermann JP, Lang F, van den Brandt J, Reichardt HM (2014) Glucocorticoids induce gastroparesis in mice through depletion of l-arginine. Endocrinology 155:3899–3908

    Article  PubMed  Google Scholar 

  • Ren C, Wang F, Li G, Jiao Q, Bai J, Yu D, Hao W, Wang R, Cao J-M (2008) Nerve sprouting suppresses myocardial Ito and IK1 channels and increases severity to ventricular fibrillation in rat. Auton Neurosci 144:22–29

    Article  CAS  PubMed  Google Scholar 

  • Rhee K-J, Cheng H, Harris A, Morin C, Kaper JB, Hecht G (2011) Determination of spatial and temporal colonization of enteropathogenic E. coli and enterohemorrhagic E. coli in mice using bioluminescent in vivo imaging. Gut Microbes 2:34–41

    Article  PubMed  PubMed Central  Google Scholar 

  • Robey TE, Murry CE (2008) Absence of regeneration in the MRL/MpJ mouse heart following infarction or cryoinjury. Cardiovasc Pathol 17:6–13

    Article  CAS  PubMed  Google Scholar 

  • Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Munnink BBO, De Meulder D, Van Amerongen G, Van Den Brand J, Okba NM (2020) Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science 368:1012–1015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rossato MF, Oliveira SM, Trevisan G, Rotta M, Machado P, Martins MA, Ferreira J (2015) Structural improvement of compounds with analgesic activity: AC-MPF4, a compound with mixed anti-inflammatory and antinociceptive activity via opioid receptor. Pharmacol Biochem Behav 129:72–78

    Article  CAS  PubMed  Google Scholar 

  • Ruggeri BA, Camp F, Miknyoczki S (2014) Animal models of disease: pre-clinical animal models of cancer and their applications and utility in drug discovery. Biochem Pharmacol 87:150–161

    Article  CAS  PubMed  Google Scholar 

  • Saito T, Matsuba Y, Mihira N, Takano J, Nilsson P, Itohara S, Iwata N, Saido TC (2014) Single App knock-in mouse models of Alzheimer’s disease. Nat Neurosci 17:661–663

    Article  CAS  PubMed  Google Scholar 

  • Sarkar S, Chawla-Sarkar M, Young D, Nishiyama K, Rayborn ME, Hollyfield JG, Sen S (2004) Myocardial cell death and regeneration during progression of cardiac hypertrophy to heart failure. J Biol Chem 279:52630–52642

    Article  CAS  PubMed  Google Scholar 

  • Sarma P, Kaur H, Kumar H, Mahendru D, Avti P, Bhattacharyya A, Prajapat M, Shekhar N, Kumar S, Singh R (2020) Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: a systematic review and meta-analysis. J Med Virol 92:776–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaguri H, Nilsson P, Hashimoto S, Nagata K, Saito T, De Strooper B, Hardy J, Vassar R, Winblad B, Saido TC (2017) APP mouse models for Alzheimer's disease preclinical studies. EMBO J 36:2473–2487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schachter AS, Davis KL (2000) Alzheimer’s disease. Dialogues Clin Neurosci 2:91–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schubert D, Maier B, Morawietz L, Krenn V, Kamradt T (2004) Immunization with glucose-6-phosphate isomerase induces T cell-dependent peripheral polyarthritis in genetically unaltered mice. J Immunol 172:4503–4509

    Article  CAS  PubMed  Google Scholar 

  • Scott DL, Wolfe F, Huizinga TW (2010) Rheumatoid arthritis. Lancet 376:1094–1108

    Article  PubMed  Google Scholar 

  • Sewell F, Aggarwal M, Bachler G, Broadmeadow A, Gellatly N, Moore E, Robinson S, Rooseboom M, Stevens A, Terry C (2017) The current status of exposure-driven approaches for chemical safety assessment: a cross-sector perspective. Toxicology 389:109–117

    Article  CAS  PubMed  Google Scholar 

  • Shekhawat PB, Pokharkar VB (2017) Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles. Acta Pharm Sin B 7:260–280

    Article  Google Scholar 

  • Shi Y, Lin S, Staats KA, Li Y, Chang W-H, Hung S-T, Hendricks E, Linares GR, Wang Y, Son EY (2018) Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons. Nat Med 24:313–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shiomi M, Ito T, Yamada S, Kawashima S, Fan J (2003) Development of an animal model for spontaneous myocardial infarction (WHHLMI rabbit). Arterioscler Thromb Vasc Biol 23:1239–1244

    Article  CAS  PubMed  Google Scholar 

  • Sia SF, Yan LM, Chin AWH, Fung K, Choy K-T, Wong AYL, Kaewpreedee P, Perera RAPM, Poon LLM, Nicholls JM, Peiris M, Yen H-L (2020) Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature 583:834–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silva LP, de Angelis CD, Bonamin F, Kushima H, Mininel FJ, Dos Santos LC, Delella FK, Felisbino SL, Vilegas W, da Rocha LRM (2015) Terminalia catappa L.: a medicinal plant from the Caribbean pharmacopeia with anti-Helicobacter pylori and antiulcer action in experimental rodent models. J Ethnopharmacol 159:285–295

    Article  Google Scholar 

  • Sim DS, Kauser K (2015) In vivo target validation using biological molecules in drug development. In: New approaches to drug discovery. Springer, Cham, pp 59–70

    Chapter  Google Scholar 

  • Singhvi G, Singh M (2011) In-vitro drug release characterization models. Int J Pharm Stud Res 2:77–84

    Google Scholar 

  • Sjolinder H, Jonsson AB (2007) Imaging of disease dynamics during meningococcal sepsis. PLoS One 2:e241

    Article  PubMed  PubMed Central  Google Scholar 

  • Smolen JS, Aletaha D, McInnes IB (2016) Rheumatoid arthritis. Lancet 388:2023–2038

    Article  CAS  PubMed  Google Scholar 

  • Song J, Zheng L, Zhang X, Feng X, Fan R, Sun L, Hong F, Zhang Y, Zhu J (2014) Upregulation of β1-adrenoceptors is involved in the formation of gastric dysmotility in the 6-hydroxydopamine rat model of Parkinson's disease. Transl Res 164:22–31

    Article  CAS  PubMed  Google Scholar 

  • Stegemann S, Leveiller F, Franchi D, De Jong H, Lindén H (2007) When poor solubility becomes an issue: from early stage to proof of concept. Eur J Pharm Sci 31:249–261

    Article  CAS  PubMed  Google Scholar 

  • Stuart JM, Townes AS, Kang AH (1984) Collagen autoimmune arthritis. Annu Rev Immunol 2:199–218

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Zhuang Z, Zheng J, Li K, Wong RL-Y, Liu D, Huang J, He J, Zhu A, Zhao J (2020a) Generation of a broadly useful model for COVID-19 pathogenesis, vaccination, and treatment. Cell 182:734–743.e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun S-H, Chen Q, Gu H-J, Yang G, Wang Y-X, Huang X-Y, Liu S-S, Zhang N-N, Li X-F, Xiong R (2020b) A mouse model of SARS-CoV-2 infection and pathogenesis. Cell Host Microbe 28:124–133.e4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sutton MGSJ, Sharpe N (2000) Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 101:2981–2988

    Article  CAS  PubMed  Google Scholar 

  • Tak PP, Gerlag DM, Aupperle KR, Van De Geest DA, Overbeek M, Bennett BL, Boyle DL, Manning AM, Firestein GS (2001) Inhibitor of nuclear factor κB kinase β is a key regulator of synovial inflammation. Arthritis Rheum 44:1897–1907

    Article  CAS  PubMed  Google Scholar 

  • Tang C, Prueksaritanont T (2010) Use of in vivo animal models to assess pharmacokinetic drug-drug interactions. Pharm Res 27:1772–1787

    Article  CAS  PubMed  Google Scholar 

  • Thalhofer CJ, Graff JW, Love-Homan L, Hickerson SM, Craft N, Beverley SM, Wilson ME (2010) In vivo imaging of transgenic Leishmania parasites in a live host. J Vis Exp 41:1980. https://doi.org/10.3791/1980

    Article  Google Scholar 

  • Thompson TN (2000) Early ADME in support of drug discovery: the role of metabolic stability studies. Curr Drug Metab 1:215–241

    Article  CAS  PubMed  Google Scholar 

  • Unsöld B, Schotola H, Jacobshagen C, Seidler T, Sossalla S, Emons J, Klede S, Knöll R, Guan K, El-Armouche A (2012) Age-dependent changes in contractile function and passive elastic properties of myocardium from mice lacking muscle LIM protein (MLP). Eur J Heart Fail 14:430–437

    Article  PubMed  Google Scholar 

  • Valgas C, de Souza SM, Smânia EF, Smânia A Jr (2007) Screening methods to determine antibacterial activity of natural products. Braz J Microbiol 38:369–380

    Article  Google Scholar 

  • Vincent TL, Williams RO, Maciewicz R, Silman A, Garside P (2012) Mapping pathogenesis of arthritis through small animal models. Rheumatology (Oxford) 51:1931–1941

    Article  PubMed  Google Scholar 

  • Wang J, Zhang T, Zhu L, Ma C, Wang S (2015) Anti-ulcerogenic effect of Zuojin Pill against ethanol-induced acute gastric lesion in animal models. J Ethnopharmacol 173:459–467

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Fu Q, Dong Y, Zhou Y, Jia S, Du J, Zhao F, Wang Y, Wang X, Peng J, Yang S et al (2010) Bioluminescence imaging of Hepatitis C virus NS3/4A serine protease activity in cells and living animals. Antivir Res 8:50–56

    Article  CAS  Google Scholar 

  • Wei Y-j, Tang Y, Li J, Cui C-j, Zhang H, Zhang X-l, Zhang H, Hu S-s (2007) Cloning and expression pattern of dog SDF-1 and the implications of altered expression of SDF-1 in ischemic myocardium. Cytokine 40:52–59

    Article  CAS  PubMed  Google Scholar 

  • Welsh C, Enomoto M, Pan J, Shifrin Y, Belik J (2013) Tetrahydrobiopterin deficiency induces gastroparesis in newborn mice. Am J Physiol Gastrointest Liver Physiol 305:G47–G57

    Article  CAS  PubMed  Google Scholar 

  • Wen X, Westergard T, Pasinelli P, Trotti D (2017) Pathogenic determinants and mechanisms of ALS/FTD linked to hexanucleotide repeat expansions in the C9orf72 gene. Neurosci Lett 636:16–26

    Article  CAS  PubMed  Google Scholar 

  • WHO (1998) The World Health Report 1998: life in the 21st century a vision for all. The world health report 1998: life in the 21st century—a vision for all, p 241

    Google Scholar 

  • WHO (2020) Coronavirus disease 2019 (COVID-19) situation report. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports

  • Witcomb LA, Collins JW, McCarthy AJ, Frankel G, Taylor PW (2015) Bioluminescent imaging reveals novel patterns of colonization and invasion in systemic Escherichia coli K1 experimental infection in the neonatal rat. Infect Immun 83:4528–4540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Witcomb LA, Czupryna J, Francis KP, Frankel G, Taylor PW (2017) Non-invasive three-dimensional imaging of Escherichia coli K1 infection using diffuse light imaging tomography combined with micro-computed tomography. Methods 127:62–68

    Article  CAS  PubMed  Google Scholar 

  • Woolsey C, Borisevich V, Prasad AN, Agans KN, Deer DJ, Dobias NS, Heymann JC, Foster SL, Levine CB, Medina L (2020) Establishment of an African green monkey model for COVID-19. BioRxiv. 10.1101/2020.05.17.100289. Update in: Nat Immunol. 2020 Nov 24;: PMID: 32511377; PMCID: PMC7263506

    Google Scholar 

  • Woolsey C, Borisevich V, Prasad AN, Agans KN, Deer DJ, Dobias NS, Heymann JC, Foster SL, Levine CB, Medina L (2021) Establishment of an African green monkey model for COVID-19 and protection against re-infection. Nat Immunol 22:86–98

    Article  CAS  PubMed  Google Scholar 

  • Yao Y-F, Wang Z-J, Jiang R-D, Hu X, Zhang H-J, Zhou Y-W, Gao G, Chen Y, Peng Y, Liu M-Q (2021) Protective efficacy of inactivated vaccine against SARS-CoV-2 infection in mice and non-human primates. Virol Sin 36:879–889. https://doi.org/10.1007/s12250-021-00376-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu P, Qi F, Xu Y, Li F, Liu P, Liu J, Bao L, Deng W, Gao H, Xiang Z (2020) Age related rhesus macaque models of COVID-19. Animal Model Exp Med 3:93–97

    Article  PubMed  PubMed Central  Google Scholar 

  • Yue L, Melnyk P, Gaspo R, Wang Z, Nattel S (1999) Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation. Circ Res 84:776–784

    Article  CAS  PubMed  Google Scholar 

  • Zeng L, Hu Q, Wang X, Mansoor A, Lee J, Feygin J, Zhang G, Suntharalingam P, Boozer S, Mhashilkar A (2007) Bioenergetic and functional consequences of bone marrow–derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Circulation 115:1866–1875

    Article  PubMed  Google Scholar 

  • Zhang Y, Huang K, Wang T, Deng F, Gong W, Hui X, Zhao Y, He X, Li C, Zhang Q (2021) SARS-CoV-2 rapidly adapts in aged BALB/c mice and induces typical pneumonia. J Virol 95:e02477–e02420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Z, Gong S, Wang S, Ma C (2015) Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway. Int Immunopharmacol 28:588–595

    Article  CAS  PubMed  Google Scholar 

  • Zheng L-F, Wang Z-Y, Li X-f, Song J, Hong F, Lian H, Wang Q, Feng X-Y, Tang Y-y, Zhang Y (2011) Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson’s disease. Brain Res 1420:59–67

    Article  CAS  PubMed  Google Scholar 

  • Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R (2020) A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382:727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zon LI, Peterson RT (2005) In vivo drug discovery in the zebrafish. Nat Rev Drug Discov 4:35–44

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Asthana, S., Shukla, V., Tripathi, A. (2023). In Vivo Models for Evaluation of Drug Efficacy: Demand and Challenges. In: Rajput, V.S., Runthala, A. (eds) Drugs and a Methodological Compendium . Springer, Singapore. https://doi.org/10.1007/978-981-19-7952-1_5

Download citation

Publish with us

Policies and ethics