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

Affiliation
Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota PMB 1023, Nigeria;(G.A.);(G.O.);(O.O.A.)
Adebayo, Glory;
Affiliation
Department of Biological Sciences, College of Science and Technology, Covenant University, Ota PMB 1023, Nigeria
Ayanda, Opeyemi I.;
Affiliation
Swiss Tropical and Public Health Institute, Kreuzstrasse 2, CH-4123 Allschwil, Switzerland;(M.R.);(P.M.)
Rottmann, Matthias;
ORCID
0000-0002-3888-2366
Affiliation
Biochemistry and Nutrition Division, Nigerian Institute of Medical Research, Yaba PMB 2013, Nigeria;(O.S.A.);(O.A.)
Ajibaye, Olusola S.;
Affiliation
Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota PMB 1023, Nigeria;(G.A.);(G.O.);(O.O.A.)
Oduselu, Gbolahan;
Affiliation
Department of Biochemistry and Sports Science, College of Natural Sciences, Makerere University, Kampala P.O. Box 7062, Uganda;
Mulindwa, Julius;
ORCID
0000-0002-3422-3478
Affiliation
Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota PMB 1023, Nigeria;(G.A.);(G.O.);(O.O.A.)
Ajani, Olayinka O.;
Affiliation
Biochemistry and Nutrition Division, Nigerian Institute of Medical Research, Yaba PMB 2013, Nigeria;(O.S.A.);(O.A.)
Aina, Oluwagbemiga;
ORCID
0000-0003-3122-1941
Affiliation
Swiss Tropical and Public Health Institute, Kreuzstrasse 2, CH-4123 Allschwil, Switzerland;(M.R.);(P.M.)
Mäser, Pascal;
Affiliation
Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota PMB 1023, Nigeria;(G.A.);(G.O.);(O.O.A.)
Adebiyi, Ezekiel

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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