The Importance of Murine Models in Determining In Vivo Pharmacokinetics, Safety, and Efficacy in Antimalarial Drug Discovery

被引:0
作者
Adebayo, Glory [1 ,2 ,3 ]
Ayanda, Opeyemi I. [2 ]
Rottmann, Matthias [4 ]
Ajibaye, Olusola S. [3 ]
Oduselu, Gbolahan [1 ,5 ]
Mulindwa, Julius [6 ]
Ajani, Olayinka O. [1 ,5 ]
Aina, Oluwagbemiga [3 ]
Maser, Pascal [4 ]
Adebiyi, Ezekiel [1 ,7 ,8 ,9 ]
机构
[1] Covenant Univ, Covenant Univ Bioinformat Res CUBRe, PMB 1023, Ota, Nigeria
[2] Covenant Univ, Coll Sci & Technol, Dept Biol Sci, PMB 1023, Ota, Nigeria
[3] Nigerian Inst Med Res, Biochem & Nutr Div, PMB 2013, Yaba, Nigeria
[4] Swiss Trop & Publ Hlth Inst, Kreuzstr 2, CH-4123 Allschwil, Switzerland
[5] Covenant Univ, Coll Sci & Technol, Dept Chem, PMB 1023, Ota, Nigeria
[6] Makerere Univ, Coll Nat Sci, Dept Biochem & Sports Sci, POB 7062, Kampala, Uganda
[7] German Canc Res Ctr, Div Appl Bioinformat, D-69120 Heidelberg, Germany
[8] African Ctr Excellence Bioinformat & Data Intens S, POB 7062, Kampala, Uganda
[9] Makerere Univ, Infect Dis Inst, POB 22418, Kampala, Uganda
关键词
antimalaria; drug discovery; efficacy assessments; murine models; pharmacokinetics; MOUSE MODELS; MALARIA; MICE; VITRO; RATS; COMBINATION; INFECTIONS; INDUCTION; PROTECTS; OUTCOMES;
D O I
10.3390/ph18030424
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
New chemical entities are constantly being investigated towards antimalarial drug discovery, and they require animal models for toxicity and efficacy testing. Murine models show physiological similarities to humans and are therefore indispensable in the search for novel antimalarial drugs. They provide a preclinical basis (following in vitro assessments of newly identified lead compounds) for further assessment in the drug development pipeline. Specific mouse strains, non-humanized and humanized, have successfully been infected with rodent Plasmodium species and the human Plasmodium species, respectively. Infected mice provide a platform for the assessment of treatment options being sought. In vivo pharmacokinetic evaluations are necessary when determining the fate of potential antimalarials in addition to the efficacy assessment of these chemical entities. This review describes the role of murine models in the drug development pipeline. It also explains some in vivo pharmacokinetic, safety, and efficacy parameters necessary for making appropriate choices of lead compounds in antimalarial drug discovery. Despite the advantages of murine models in antimalarial drug discovery, certain limitations are also highlighted.
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页数:28
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