RESUMEN
A strong scientific rationale exists for conducting clinical pharmacology studies in target populations because local factors such as genetics, environment, comorbidities, and diet can affect variability in drug responses. However, clinical pharmacology studies are not widely conducted in sub-Saharan Africa, in part due to limitations in technical expertise and infrastructure. Since 2012, a novel public-private partnership model involving research institutions and a pharmaceutical company has been applied to developing increased capability for clinical pharmacology research in multiple African countries.
Asunto(s)
Investigación Biomédica/tendencias , Farmacología Clínica/tendencias , Asociación entre el Sector Público-Privado/tendencias , África del Sur del Sahara/epidemiología , Investigación Biomédica/métodos , Ensayos Clínicos como Asunto/métodos , Humanos , Cooperación Internacional , Farmacogenética/métodos , Farmacogenética/tendencias , Farmacología Clínica/métodosRESUMEN
Warfarin, the only available oral coumarin anticoagulant in South Africa, is widely prescribed for the prevention and management of arterial and venous thrombo-embolism. It has a narrow therapeutic index and a wide inter-individual variability in therapeutic response. Genetic polymorphism of the VKORC1 and CYP2C9 genes, as well as clinical factors such as age, gender, body mass index and interacting drugs explain less than 55% of variability in warfarin dose requirements. True warfarin resistance is rare (< 0.1%) and is defined as warfarin requirements greater than 70 mg per week to maintain the international normalised ratio (INR) in the target therapeutic range. As hereditary warfarin resistance is rare, non-adherence, laboratory errors and interactions should be excluded in patients with persistent sub-therapeutic INR levels. Pharmacogenetic models to estimate individualised warfarin doses do not take into account the mutations associated with warfarin resistance. In patients with presumed warfarin resistance, higher doses that maintain the INR in the target therapeutic range should be given, and the INR closely and regularly monitored.