Cross-disciplinary mathematical modelling to benefit healthcare - could clinical pharmacology play an enabling role?

Clinical pharmacology is often the nexus in any cross-disciplinary team that is seeking solutions for human healthcare issues. The use and application of real-world data and artificial intelligence to better understand our ecosystem has influenced our view at the world and how we do things. This has resulted in remarkable advancements in the healthcare space and development of personalized medicines with great attributes from the application of models and simulations, contributing to a more efficient healthcare development process.

Aspalathin-rich green rooibos tea in combination with glyburide and atorvastatin enhances lipid metabolism in a mouse model.

Rooibos (), an indigenous South African plant and its major flavonoid, aspalathin, exhibited positive effects on glycemia and dyslipidemia in animal studies. Limited evidence exists on the effects of rooibos extract taken in combination with oral hypoglycemic and lipid-lowering medications. This study investigated the combined effects of a pharmaceutical grade aspalathin-rich green rooibos extract (GRT) with the sulfonylurea, glyburide, and atorvastatin in a type 2 diabetic () mouse model.

Mycobacteriophages to Treat Tuberculosis: Dream or Delusion?

Rates of antimicrobial resistance are increasing globally while the pipeline of new antibiotics is drying up, putting patients with disease caused by drug-resistant bacteria at increased risk of complications and death. The growing costs for diagnosis and management of drug resistance threaten tuberculosis control where the disease is endemic and resources limited. Bacteriophages are viruses that attack bacteria.

Needs-driven talent and competency development for the next generation of regulatory scientists in Africa.

Capacity building programmes for African regulators should link education, training and research with career development in an approach that combines an academic base and experiential learning aligned within a competency framework. A regulatory ecosystem that engages with a broad range of stakeholders will mean that expertise in the ever-expanding field of regulatory science filters into teaching and research in a symbiotic way. In this way capacity development interventions will be a collaborative approach between the learning context (academic and training institutions) and the performance context (regulatory agencies and industry), which will ultimately best serve the patients.

Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.

Oral therapeutics used to treat type 2 diabetes and cardiovascular disease often fail to prevent the progression of disease and their comorbidities. Rooibos (Aspalathus linearis), an endemic South African plant used as an herbal tea, has demonstrated positive effects on glycemia and hypercholesterolemia. However, the treatment efficacy of rooibos extract in combination with conventional hypoglycemic and hypolipidemic medications on blood glucose and lipid profiles has not been established.

Investigation of CYP2B6, 3A4 and β-esterase interactions of Withania somnifera (L.) dunal in human liver microsomes and HepG2 cells.

Ethnopharmacological Relevance: Withania somnifera (L.) Dunal (Solanaceae) is a traditional herb, used in African indigenous systems of medicine for the treatment of various diseases (including HIV/AIDS and tuberculosis). The relevance of clinically significant interactions of Withania with ARVs and anti-TB drugs needs to be investigated.

Assessment of the Interaction Potential of (L.) Extracts on CYP2B6, 3A4, and Rifampicin Metabolism.

L. or basilicum is a common culinary herb, used as a traditional medicine for various medical conditions including HIV/AIDS and tuberculosis, in Africa. The objective of this study was to evaluate the effect of methanol, ethanol, aqueous and ethyl acetate extracts of the dried leaves and inflorescence of , on the activity of cytochrome P450 enzymes (CYPs) CYP2B6 and 3A4, as well as esterase-mediated metabolism of rifampicin to 25--desacetyl rifampicin (25ODESRIF).

Pharmacokinetic Interaction of Green Rooibos Extract With Atorvastatin and Metformin in Rats.

An aspalathin-rich green rooibos extract (Afriplex GRT™) has demonstrated anti-diabetic and hypolipidemic properties, while also moderately inhibiting CYP3A4 activity, suggesting a potential for herb-drug interaction. The present study, therefore, evaluated the effects of orally administered GRT on the pharmacokinetics of atorvastatin and metformin in Wistar rats. Wistar rats were orally treated with GRT (50 mg/kg BW), atorvastatin (40 mg/kg BW) or metformin (150 mg/kg BW) alone or 50 mg/kg BW GRT in combination with 40 mg/kg BW atorvastatin or 150 mg/kg BW metformin.

Adverse Drug Reactions in Paediatric In-Patients in a South African Tertiary Hospital.

Background: The prevalence of adverse drug reaction (ADR) rates in children in sub-Saharan Africa is unknown.

Objectives: To describe the prevalence of ADRs in paediatric in-patients at a tertiary hospital in South Africa.

Methods: This is a prospective study during a 3-month study period.

Off-label Use in Ambulatory Paediatric Clinics in a Central South African Hospital.

Aim: The aim of this article was to determine off-label (OL) use in paediatric ambulatory clinics in a South African central hospital.

Patients And Methods: OL medicine events were documented in three paediatric clinics (general, highly specialized and dedicated HIV paediatric clinics) at Tygerberg Hospital, South Africa, and analysed according to South African medicine registration information.

Results: There were 2167 medicine events for 658 children.

B-cell and T-cell activation in South African HIV-1-positive non-Hodgkin's lymphoma patients.

Background: Altered immune mechanisms play a critical role in the pathogenesis of non-Hodgkin's lymphoma (NHL). HIV-1 (HIV) infection is associated with a state of excessive T-cell activation, which can lead to increased T-cell turnover and lymph node fibrosis.

Objectives: This study aimed to determine the serum levels of circulating B-cell activation markers, and the expression of T-cell activation and regulatory markers in HIV-positive NHL patients.

Lopinavir serum concentrations of critically ill infants: a pharmacokinetic investigation in South Africa.

The role of therapeutic drug monitoring in pediatric antiretroviral therapy is unclear. A little pharmacokinetic datum from clinical practice exists beyond controlled approval studies including clinically stable children. The aim of this study is to quantify LPV exposure of critically ill infants in an ICU and-by identifying risk factors for inadequate exposure-to define sensible indications for TDM in pediatric HIV care; in addition, assume total drug adherence in ICU to compare LPV exposure with a setting of unknown adherence.

Evaluation of the Effectiveness of Dose Individualization to Achieve Therapeutic Vancomycin Concentrations.

The glycopeptide antibiotic vancomycin is used for treatment of methicillin-resistant Gram-positive cocci. Adequate vancomycin plasma concentrations are related to bacterial cure. However, inter- and intrapatient variability make it difficult to achieve therapeutic vancomycin concentrations.

Critical evaluation of causality assessment of herb-drug interactions in patients.

The aim of this review was to assess the severity of adverse drug reactions (ADRs) due to herb-drug interactions (HDI) in patients taking herbs and prescribed medications based on published evidence. Electronic databases of PubMed, the Cochrane Library, Medline and Scopus were searched for randomized or nonrandomized clinical studies, case-control and case reports of HDI. The data were extracted and the causal relationship of ADRs as consequences of HDI assessed using Horn's drug interaction probability scale or Roussel Uclaf Causality Assessment Method scoring systems.

Association between Health-Related Quality of Life and Medication Adherence in Pulmonary Tuberculosis in South Africa.

Health-related quality of life (HRQOL) and adherence to treatment are two often inter-related concepts that have implications for patient management and care. Tuberculosis (TB) and its treatment present a major public health concern in South Africa. The study aimed to evaluate the association between HRQOL and adherence in TB patients in South Africa.

MicroRNA-655-3p regulates Echinacea purpurea mediated activation of ABCG2.

1. The aim of this study was to investigate the regulatory effect of Echinacea purpurea (EP) on efflux transporters ABCB1 and ABCG2 and to identify specific microRNAs contributing to their post-transcriptional regulation. 2.

Health-related quality of life in South African patients with pulmonary tuberculosis.

Background: The evaluation of patient-reported health-related quality of life (HRQOL) in pulmonary tuberculosis (TB) contributes to a comprehensive understanding of the burden associated with this disease. The aim of this study was to assess the overall impact of TB on the health status and on single health domains identified in the WHO definition of health, including physical, mental and social health aspects.

Methods: Four instruments for HRQOL evaluation were applied in a longitudinal multicentre study during six-month standard TB treatment in South Africa.

Inhibitory Interactions of Aspalathus linearis (Rooibos) Extracts and Compounds, Aspalathin and Z-2-(β-d-Glucopyranosyloxy)-3-phenylpropenoic Acid, on Cytochromes Metabolizing Hypoglycemic and Hypolipidemic Drugs.

Rooibos extract, due to its glucose and lipid lowering effects, has potential as a nutraceutical for improvement of metabolic dysfunction. Potential herb-drug interactions as a result of the use of natural products are of increasing concern. Cytochrome P450 enzymes, CYP2C8, CYP2C9, and CYP3A4, are important in the metabolism of hypoglycemic drugs, such as thiazolidinediones (TZDs) and sulfonylureas, and hypocholesterolemic drugs, such as atorvastatin.

How to Evaluate Health-Related Quality of Life and Its Association with Medication Adherence in Pulmonary Tuberculosis - Designing a Prospective Observational Study in South Africa.

Introduction: Health-related quality of life (HRQOL) has become an important measure to identify and shape effective and patient-relevant healthcare interventions innovations through outcomes. Adherence to tuberculosis (TB) treatment is a public health concern. The main objective of this research is to develop a study design for evaluation of HRQOL and its association with medication adherence in TB in South Africa.

Health-related quality of life and its association with medication adherence in active pulmonary tuberculosis- a systematic review of global literature with focus on South Africa.

Introduction: Tuberculosis (TB) is a leading cause of morbidity and mortality in South Africa. Clinical parameters are important objective outcomes in TB; however they often are not directly correlated with subjective well-being of the patient, but can be assessed using patient-reported outcome (PRO) measures. Health-related quality of life (HRQOL) is a specific PRO generally multi-dimensional in nature and includes physical, mental and social health domains.

In vivo monitoring of urea cycle activity with (13)C-acetate as a tracer of ureagenesis.

Background: The hepatic urea cycle is the main metabolic pathway for detoxification of ammonia. Inborn errors of urea cycle function present with severe hyperammonemia and a high case fatality rate. Long-term prognosis depends on the residual activity of the defective enzyme.

N-acetyltransferase genotypes and the pharmacokinetics and tolerability of para-aminosalicylic acid in patients with drug-resistant pulmonary tuberculosis.

The aim of this study was to examine the relationships between N-acetyltransferase genotypes, pharmacokinetics, and tolerability of granular slow-release para-aminosalicylic acid (GSR-PAS) in tuberculosis patients. The study was a randomized, two-period, open-label, crossover design wherein each patient received 4 g GSR-PAS twice daily or 8 g once daily alternately. The PAS concentration-time profiles were modeled by a one-compartment disposition model with three transit compartments in series to describe its absorption.