RESUMEN
AIM: Oxycodone is partly metabolized to the active metabolite oxymorphone by hepatic CYP2D6 in the liver. Significant genetic variability in CYP2D6 activity affects oxymorphone formation. This study aimed to associate CYP2D6 genotype and oxycodone's metabolism. METHODS: 30 children were administered oral oxycodone postoperatively. Plasma levels of oxycodone and oxymorphone, and CYP2D6 genotype were analyzed. CYP2D6 genotype and oxycodone metabolism phenotype were determined based on CYP2D6 total activity score (TAS) and metabolism phenotype: poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM) or ultrarapid metabolizer (UM). RESULTS: Compared with PM/IM subjects, significantly greater oxymorphone exposure was seen in EM subjects (p = 0.02 for Cmax, p = 0.016 for AUC0-6 and p = 0.026 for AUC0-24). Similarly, higher TAS value was found to be associated with greater oxymorphone exposure. Higher conversion of oxycodone to oxymorphone was observed in EM subjects compared with PM/IM subjects (p = 0.0007 for Cmax, p = 0.001 for AUC0-6 and p = 0.004 for AUC0-24). CONCLUSION: CYP2D6 phenotypes explain metabolism of oxycodone in children, and oxymorphone exposure is higher in CYP2D6 EM phenotype. Further studies are needed to predict the occurrence of adverse event and tailor oxycodone dose for a specific CYP2D6 phenotype.
Asunto(s)
Analgésicos Opioides/farmacocinética , Citocromo P-450 CYP2D6/genética , Oxicodona/farmacocinética , Dolor Postoperatorio/sangre , Dolor Postoperatorio/genética , Farmacogenética/métodos , Administración Oral , Adolescente , Analgésicos Opioides/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Masculino , Oxicodona/administración & dosificación , Dolor Postoperatorio/prevención & control , Proyectos Piloto , Estudios ProspectivosRESUMEN
The technique of choice for surgical correction of pectus excavatum is the Nuss procedure, a minimally invasive technique in which rigid metal bars are placed transthoracically beneath the sternum and costal cartilages until permanent remodeling of the chest wall has occurred. Intraoperatively, anesthesia focuses on three areas: the potential for catastrophic blood loss caused by perforation of large capacitance vessels and the heart, the potential for malignant arrhythmias, and the consequences of bilateral iatrogenic pneumothoraces. Postoperatively, analgesia is institutionally dependent and controversial, based on usage and type of regional anesthesia. The necessity of multimodal analgesic techniques creates a common ground across different hospital systems.