RESUMO
Tacrolimus (TAC) is highly effective for the prevention of acute organ rejection. However, its clinical use may be challenging due to its large interindividual pharmacokinetic variability, which can be partially explained by genetic variations in TAC-metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of genetic and clinical factors on TAC pharmacokinetic variability in 21 stable pediatric renal transplant patients. This study was nested in a previous Prograf to Advagraf conversion clinical trial. CYP3A5, ABCB1 and two POR genotypes were assessed by real-time PCR. The impact on TAC pharmacokinetics of individual genetic variants on CYP3A5 nonexpressors was evaluated by genetic score. Explicative models for TAC AUC0-24h, Cmax and Cmin after Advagraf were developed by linear regression. The built genetic scores explain 13.7 and 26.5% of the total AUC0-24h and Cmin total variability, respectively. Patients genetic information should be considered to monitorizate and predict TAC exposure.
Assuntos
Citocromo P-450 CYP3A/genética , Sistema Enzimático do Citocromo P-450/genética , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Tacrolimo/farmacocinética , Tacrolimo/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Criança , Feminino , Variação Genética/genética , Genótipo , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/genética , Humanos , Transplante de Rim/métodos , MasculinoRESUMO
By using the results of seven carbon substrate assimilation tests from the Biotype 100 system (bioMérieux, Marcy-l'Etoile, France), we correctly identified 79 (85.9%) of 92 Brucella strains tested. The specificity of the method varied from 97.4 to 100% depending on the species. Although a biological safety cabinet must be used, this method represents an easy and fast alternative for the identification of Brucella species.
