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- Dandara, C, et al.
(författare)
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African Pharmacogenomics Consortium: Consolidating pharmacogenomics knowledge, capacity development and translation in Africa: Consolidating pharmacogenomics knowledge, capacity development and translation in Africa
- 2019
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Ingår i: AAS open research. - : F1000 Research Ltd. - 2515-9321. ; 2, s. 19-
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Tidskriftsartikel (refereegranskat)abstract
- The African Pharmacogenomics Consortium (APC) was formally launched on the 6th September 2018. This white paper outlines its vision, and objectives towards addressing challenges of conducting and applying pharmacogenomics in Africa and identifies opportunities for advancement of individualized drugs use on the continent. Africa, especially south of the Sahara, is beset with a huge burden of infectious diseases with much co-morbidity whose multiplicity and intersection are major challenges in achieving the sustainable development goals (SDG), SDG3, on health and wellness. The profile of drugs commonly used in African populations lead to a different spectrum of adverse drug reactions (ADRs) when compared to other parts of the world. Coupled with the genetic diversity among Africans, the APC is established to promote pharmacogenomics research and its clinical implementation for safe and effective use of medicine in the continent. Variation in the way patients respond to treatment is mainly due to differences in activity of enzymes and transporters involved in pathways associated with each drug’s disposition. Knowledge of pharmacogenomics, therefore, helps in identifying genetic variants in these proteins and their functional effects. Africa needs to consolidate its pharmacogenomics expertise and technological platforms to bring pharmacogenomics to use.
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- Desta, Z, et al.
(författare)
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PharmVar GeneFocus: CYP2B6
- 2021
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Ingår i: Clinical pharmacology and therapeutics. - : Wiley. - 1532-6535 .- 0009-9236. ; 110:1, s. 82-97
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Ross, I. L., et al.
(författare)
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Investigation of glucocorticoid receptor polymorphisms in relation to metabolic parameters in Addison's disease
- 2013
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 168, s. 403-412
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Tidskriftsartikel (refereegranskat)abstract
- Background Uncertainty exists whether glucocorticoid receptor (GCR) polymorphisms play a role in steroid-related side effects in Addison's disease (AD) patients on hydrocortisone. The polymorphisms Bcll and N363S appear to increase sensitivity to cortisol, while the ER22/23EK polymorphism has been associated with resistance to cortisol. Method One hundred and forty seven AD patients, and gender, and ethnicity-matched controls were recruited in South Africa. Three polymorphisms in the GCR were studied, using PCR followed by restriction fragment length analysis. Associations with BMI, lipids, glucose and inflammatory markers were investigated. Results In both patients and controls, the Bcll polymorphism occurred more frequently in whites than in other ethnic groups studied but was not associated with any of the metabolic parameters tested. The ER22/23EK polymorphism was associated with an increased BMI in both patients (29.4 vs 24.7kg/m2) and control subjects (26.3 vs 24.2kg/m2). The ER22/23EK polymorphism was also associated with lower LDL cholesterol in control subjects (3.46 vs 3.93mmol/l) and in patients (3.52 vs 4.10mmol/l). N363S was associated with increased BMI in controls 29.9kg/m2 vs wild type 24.8kg/m2. Median hydrocortisone doses were greater in patients heterozygous for either ER22/23EK 30.0mg or N363S 25.0mg polymorphisms than in wild type patients 20.0mg (both comparisons). Conclusion Alterations in lipids, BMI and hydrocortisone dose were associated with two polymorphisms. Further larger studies are warranted to corroborate these findings.
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- Viljoen, M., et al.
(författare)
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Influence of CYP2B6 516G > T polymorphism and interoccasion variability (IOV) on the population pharmacokinetics of efavirenz in HIV-infected South African children
- 2012
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 68:4, s. 339-347
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the influence of CYP2B6 516G > T polymorphism, as a covariate, and of interoccasion variability (IOV) on the oral clearance (CL/F) of efavirenz (EFV) in treatment-na < ve black South African children over a period of 24 months post-antiretroviral therapy (ART) initiation. HIV-infected black children (n = 60, aged 3-16 years), with no prior exposure to ART, eligible to commence ART and attending an outpatient clinic were enrolled into this study. Blood samples were taken at mid-dose interval at 1, 3, 6, 12, 18 and 24 months post-ART initiation. EFV plasma samples were determined with an adapted and validated LC/MS/MS method. Genotyping of the CYP2B6 G516T single nucleotide polymorphism (SNP) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). NONMEM was used for the population pharmacokinetic modelling. EFV concentrations below 1 mu g/mL accounted for 18% (116/649), EFV concentrations > 4 mu g/mL accounted for 29.5% (192/649) and concentrations within the therapeutic range (1-4 mu g/mL) represented 52.5% (341/649) of all the samples determined. The covariates age, weight and CYP2B6 G516Tgenotype were included in the final model with population estimates for CL/F determined as 2.46, 4.60 and 7.33 L/h for the T/T, G/T and G/G genotype groups respectively. The inclusion of both age and weight to predict accurate EFV CL values for the respective genotype groups within this paediatric population was required, whereas the addition of gender and body surface area did not improve the predictions. The importance of introducing IOV in a PK model for a longitudinal study with sparsely collected data was again highlighted by this investigation.
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