Publications by authors named "Roslyn Thelingwani"

We analyzed parentage data collected over a ten-year period in a Zimbabwean DNA testing laboratory. Parentage case types, prevalence, exclusion data, mutations rates and observed genotyping irregularities were analyzed. We report analysis results from 1303 cases.

View Article and Find Full Text PDF
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.
View Article and Find Full Text PDF

Pharmacogenomic testing may be used to improve treatment outcomes and reduce the frequency of adverse drug reactions (ADRs). Population specific, targeted pharmacogenetics (PGx) panel-based testing methods enable sensitive, accurate and economical implementation of precision medicine. We evaluated the analytical performance of the GenoPharm® custom open array platform which evaluates 120 SNPs across 46 pharmacogenes.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Dapsone is employed for both non-dermatological and dermatological indications but with non-existent population pharmacokinetics (popPK) data in Nigerians. This study was therefore designed to develop a popPK model in Nigerians. Non-compartmental analysis and nonlinear mixed effects modelling were utilized for data analysis.

View Article and Find Full Text PDF
Article Synopsis
  • * A study involving 40 breast cancer patients in Zimbabwe found that many had genetic variants (polymorphisms) in CYP2D6 that affect drug metabolism, leading to lower endoxifen levels.
  • * Results showed that 55% of participants had endoxifen concentrations below the therapeutic threshold, highlighting a significant relationship between CYP2D6 genetic variations and endoxifen levels (with specific statistical significance).
View Article and Find Full Text PDF

Pain is a common cause of hospitalization in sickle cell disease (SCD) patients. Failure to effectively control pain remains a challenge in patient care. The authors conducted a cross-sectional study to determine the effect of and polymorphisms on pain management in 106 Zimbabwean SCD patients.

View Article and Find Full Text PDF
Article Synopsis
  • 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.
View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

In this study, we aimed to evaluate the utility of endogenous 1β-hydroxy-deoxycholic acid/total deoxycholic acid ratio (1β-OH-DCA/ToDCA) in spot urine as a surrogate marker of cytochrome P450 3A (CYP3A) activity in the assessment inhibition-based drug-drug interactions in healthy volunteers. This was accomplished through an open-label, three-treatment parallel-arm study in healthy male volunteers from Zimbabwe. Each group received itraconazole (ITZ; 100 mg once daily; = 10), fluconazole (FKZ; 50 mg once daily; = 9), or alprazolam (APZ; 1 mg once daily; = 8) orally.

View Article and Find Full Text PDF

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 PDF

Racemic 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.

View Article and Find Full Text PDF

Aim: The study sought to determine the effect of ketoconazole (KTZ) on the pharmacokinetics of praziquantel (PZQ) and on the formation of its major hydroxylated metabolites, cis- and trans-4-OH-PZQ, and X-OH-PZQ in healthy subjects.

Methods: Two treatments were evaluated by single-dose PK studies; the reference treatment was a 20 mg/kg dose of praziquantel given alone. The test treatment was a 20 mg/kg dose of praziquantel given in combination with 200 mg of ketoconazole.

View Article and Find Full Text PDF

Background: Children living with HIV who are not diagnosed in infancy often remain undiagnosed until they present with advanced disease. Provider-initiated testing and counselling (PITC) in health facilities is recommended for high-HIV-prevalence settings, but it is unclear whether this approach is sufficient to achieve universal coverage of HIV testing. We aimed to investigate the change in community burden of undiagnosed HIV infection among older children and adolescents following implementation of PITC in Harare, Zimbabwe.

View Article and Find Full Text PDF

1. Chemotherapy remains the effective way of controlling malaria infections. Many of the treatments have been rendered ineffective as a result of drug resistance by plasmodia species as well as toxicity.

View Article and Find Full Text PDF

The safety and efficacy of herbal medicines remain major issues of concern especially in the developing world where the use is high. The World Health Organisation estimates up to 80% of the population in Africa relies on herbal medicines for treatment of many diseases. Minimum safety evaluations need to be done for both the herbal and conventional drugs, in particular when there is a high likelihood of co-administration.

View Article and Find Full Text PDF

Background And Objective: Drug resistance by Plasmodium falciparum remains a challenge in malaria chemotherapy. This paper will focus on physicochemical and drug metabolism characterization of a series of 4-aminoquinoline-3-hydroxypyridin-4-one hybrid shown to have antimalarial activity against chloroquine-resistant P. falciparum.

View Article and Find Full Text PDF

Objectives: The objectives were to determine the pharmacokinetics (PK) of artemisone and artemisone formulated in the Pheroid® drug delivery system in primates and to establish whether the formulation affects the in vitro metabolism of artemisone in human and monkey liver and intestinal microsomes.

Methods: For the PK study, a single oral dose of artemisone was administered to vervet monkeys using a crossover design. Plasma samples were analyzed by means of liquid chromatography-tandem mass spectrometry.

View Article and Find Full Text PDF

NIPRISAN(®) is a phytomedicine developed from herbal products used in folkloric practice for the management of sickle cell disease (SCD). The effect of NIPRISAN(®) was tested on human cytochrome P4503A4 drug metabolising enzyme to generate clinically significant data for its safe and efficacious use. Inhibitory activity on CYP3A4 was measured with and without the addition of NIPRISAN(®), by testing different concentrations of the product at 37 °C in reactive mixtures with ketoconazole (2.

View Article and Find Full Text PDF

1. Frutinone is an active ingredient extracted from the lipophilic fraction of the Polygala Fruticosa demonstrating various antibacterial and fungal properties. The aim of this study was to characterize its metabolism in an effort to understand metabolism based drug-herb interactions.

View Article and Find Full Text PDF

Thiabendazole (TBZ) and its major metabolite 5-hydroxythiabendazole (5OH-TBZ) were screened for potential time-dependent inhibition (TDI) against CYP1A2. Screen assays were carried out in the absence and presence of NADPH. TDI was observed with both compounds, with k(inact) and K(I) values of 0.

View Article and Find Full Text PDF