Critical assessment of phenotyping cocktails for clinical use in an African context

dc.contributor.authorLeuschner, Machel
dc.contributor.authorCromarty, Allan Duncan
dc.contributor.emailmachel.leuschner@up.ac.zaen_US
dc.date.accessioned2024-03-27T05:41:26Z
dc.date.available2024-03-27T05:41:26Z
dc.date.issued2023-07-05
dc.description† This work was presented in part as M.L.’s Ph.D. Thesis at the University of Pretoria School of Medicine (2019).en_US
dc.descriptionDATA AVAILABILITY STATEMENT : No new data were created or analyzed in this study. Data sharing is not applicable to this article.en_US
dc.description.abstractInterethnic and interindividual variability in in vivo cytochrome P450 (CYP450)-dependent metabolism and altered drug absorption via expressed transport channels such as P-glycoprotein (P-gp) contribute to the adverse drug reactions, drug–drug interaction and therapeutic failure seen in clinical practice. A cost-effective phenotyping approach could be advantageous in providing real-time information on in vivo phenotypes to assist clinicians with individualized drug therapy, especially in resource-constrained countries such as South Africa. A number of phenotyping cocktails have been developed and the aim of this study was to critically assess the feasibility of their use in a South African context. A literature search on library databases (including AccessMedicine, BMJ, ClinicalKey, MEDLINE (Ovid), PubMed, Scopus and TOXLINE) was limited to in vivo cocktails used in the human population to phenotype phase I metabolism and/or P-gp transport. The study found that the implementation of phenotyping in clinical practice is currently limited by multiple administration routes, the varying availability of probe drugs, therapeutic doses eliciting side effects, the interaction between probe drugs and extensive sampling procedures. Analytical challenges include complicated sample workup or extraction assays and impractical analytical procedures with low detection limits, analyte sensitivity and specificity. It was concluded that a single time point, non-invasive capillary sampling, combined with a low-dose probe drug cocktail, to simultaneously quantify in vivo drug and metabolite concentrations, would enhance the feasibility and cost-effectiveness of routine phenotyping in clinical practice; however, future research is needed to establish whether the quantitative bioanalysis of drugs in a capillary whole-blood matrix correlates with that of the standard plasma/serum matrixes used as a reference in the current clinical environment.en_US
dc.description.departmentPharmacologyen_US
dc.description.librarianam2024en_US
dc.description.sdgNoneen_US
dc.description.urihttps://www.mdpi.com/journal/jpmen_US
dc.identifier.citationLeuschner, M.; Cromarty, A.D. Critical Assessment of Phenotyping Cocktails for Clinical Use in an African Context. Journal of Personalized Medicine 2023, 13, 1098. https://DOI.org/10.3390/jpm13071098.en_US
dc.identifier.issn2075-4426 (online)
dc.identifier.other10.3390/jpm13071098
dc.identifier.urihttp://hdl.handle.net/2263/95371
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rights© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.en_US
dc.subjectPhenotyping cocktailen_US
dc.subjectAfrican genetic diversityen_US
dc.subjectPersonalized medicineen_US
dc.subjectCYP450en_US
dc.subjectP-glycoprotein (P-gp)en_US
dc.titleCritical assessment of phenotyping cocktails for clinical use in an African contexten_US
dc.typeArticleen_US

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Leuschner_Critical_2023.pdf
Size:
331.83 KB
Format:
Adobe Portable Document Format
Description:
Article

License bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description: