Abstract:
Interethnic 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.
