Publications by authors named "Nyasha Kapungu"
Investigation of the Differences in the Pharmacokinetics of CYP2D6 Substrates, Desipramine, and Dextromethorphan in Healthy African Subjects Carrying the Allelic Variants CYP2D6*17 and CYP2D6*29, When Compared with Normal Metabolizers.
J Clin Pharmacol
May 2024
Article Synopsis
- - The study examined how genetic variations in the CYP2D6 enzyme affect the pharmacokinetics of dextromethorphan and desipramine in healthy African volunteers, dividing subjects into three genetic cohorts.
- - Results showed that participants with CYP2D6*17*17 and CYP2D6*29*29 genotypes exhibited significantly higher drug exposure levels compared to those with the CYP2D6*1/*2 variant, indicating they metabolize these medications much slower.
- - Mild adverse effects were reported, with one instance of a moderately severe headache in a CYP2D6*17*17 individual, highlighting the need for careful dosage adjustments of CYP2D6-related drugs in African populations.
Pharmaceutical companies subject all new molecular entities to a series of in vitro metabolic characterizations that guide the selection and/or design of compounds predicted to have favorable pharmacokinetic properties in humans. Current drug metabolism research is based on liver tissue predominantly obtained from people of European origin, with limited access to tissue from people of African origin. Given the interindividual and interpopulation genomic variability in genes encoding drug-metabolizing enzymes, efficacy and safety of some drugs are poorly predicted for African populations.
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- Clinical outcomes of tamoxifen (TAM) treatment show high variability among individuals, influenced by genetic differences and other medications.
- A study involving 229 South African Black women with breast cancer found that certain genetic variants (CYP2D6*17 and CYP2D6*29) significantly impact the metabolism of TAM and its active metabolites.
- While antiretroviral therapy affected certain metabolite levels of TAM, the overall risk of significant drug interactions was considered low for patients undergoing TAM treatment.
Purpose: Women living with HIV (WLWH) and breast cancer (BC) have worse overall survival than HIV-negative women with BC, and poor adherence to prescribed tamoxifen is known to contribute to poor survival. We therefore investigated the association of HIV infection with adherence to adjuvant tamoxifen among women with localized hormone receptor (HR)-positive breast cancer in South Africa.
Methods: Among 4,097 women diagnosed with breast cancer at six hospitals in the prospective South African Breast Cancer and HIV Outcomes (SABCHO) cohort study between July 2015 and December 2020, we focused on black women with stages I-III HR-positive breast cancer who were prescribed 20 mg of adjuvant tamoxifen daily.
We conducted a clinical study to determine the effect of efavirenz and ritonavir on the pharmacokinetics of R- and S-PZQ in healthy male participants. This was toward evaluating the risk of drug-drug interactions, which may occur after PZQ administration to HIV patients on efavirenz or ritonavir containing regimens. A non-randomized, open-label, single-dose, one sequence crossover study with 2 arms was conducted.
View Article and Find Full Text PDFRacemic praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis. R-Praziquantel (R-PZQ) has been shown as the therapeutic form, whereas S-PZQ is less efficacious and responsible for the bitter taste of the tablet. This study aimed at investigating the metabolism of R- and S-PZQ as this could have implications on efficacy and safety of racemate and R-PZQ specific formulations under development.
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