Pharmacogenomics
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Observational Study
Advanced cancer pain: the search for genetic factors correlated with interindividual variability in opioid requirement.
To assess association between genetic variants and opioid requirement in cancer patients. ⋯ Patients with the combined OPRM1 118AG/GG and COMT 472GG genotype required 50% higher dose increase for sufficient analgesia.
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Large interindividual variability in morphine pharmacokinetics (PK) could contribute to variability in morphine analgesia and adverse events. Respiratory depression (RD) and postoperative nausea and vomiting (PONV) are significant adverse drug response of intravenous morphine in the perioperative setting limiting its efficacy in achieving adequate surgical pain relief. OCT1 is a transporter in the liver that transports morphine from the bloodstream into hepatocytes. Earlier we reported association of genetic polymorphisms in OCT1 with morphine PK, and lower morphine clearance in Caucasian children as compared with African-American (AA) children. The aim of this study is to identify the association between common OCT1 genotypes affecting morphine's PK and clinically important postoperative morphine-related adverse outcomes. ⋯ Children with certain OCT1 genotypes are associated with higher risk for RD and PONV following morphine administration leading to prolonged hospital stay. The OCT1 transporters' effects on morphine's PK could explain this association.
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Multicenter Study Observational Study
CYP2D6 pharmacogenetic and oxycodone pharmacokinetic association study in pediatric surgical patients.
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. ⋯ 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.
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Cystic fibrosis (CF) is genetic autosomal recessive disease caused by reduced or absent function of CFTR protein. Treatments for patients with CF have primarily focused on the downstream end-organ consequences of defective CFTR. ⋯ This has recently led to the development of new CFTR mutation-specific targeted therapies for select patients with CF. This review will discuss the characteristics of the CFTR gene, the CFTR mutations that cause CF and the new mutation specific pharmacological treatments including gene therapy that are contributing to the dawning of a new era in cystic fibrosis care.
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The role of UGT1A6 and UGT2B7 polymorphisms and the impact of total drug plasma concentration in valproic acid (VPA) pharmacogenomics. ⋯ UGT1A6 and UGT2B7 genotypes were not related to significant changes in VPA metabolism, even after controlling for total drug concentration levels. Younger ages were associated with increased VPA clearance rate.