Pharmacogenomics
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Familial loading for alcohol dependence (AD) and variation in genes reported to be associated with AD or BMI were tested in a longitudinal study. ⋯ Variation at loci implicated in addiction may be influential in determining susceptibility to increased BMI in childhood and adolescence.
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Randomized Controlled Trial
Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype.
Determine whether SNPs of OPRM1 118A>G (asn(40)asp), COMT 472G>A (val(158)met) and ARRB2 8622C>T are associated with morphine rescue in newborns on mechanical ventilation. ⋯ Combined OPRM1 118A>G and COMT 472G>A genotype might serve as a predictor for the need of rescue morphine in premature and term newborns on mechanical ventilation.
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Large interindividual variability in morphine pharmacokinetics could contribute to variability in morphine analgesia and adverse events. ⋯ Our data suggest that besides bodyweight, OCT1 and ABCC3 genotypes play a significant role in the pharmacokinetics of intravenous morphine and its metabolites in children.
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To investigate the pharmacokinetics of voriconazole when administered to HIV-positive patients receiving treatment with atazanavir-containing therapies according to CYP2C19 genotype. ⋯ Voriconazole exposure was variable but Ctrough levels were above 1000 ng/ml in all patients; one CYP2C19 intermediate metabolizer required lower doses of voriconazole (50 mg twice daily) to obtain satisfactory drug concentrations. Atazanavir and ritonavir plasma levels were moderately reduced (area under the curve: -23 and -26%, respectively); raltegravir exposure seemed increased by voriconazole administration (area under the curve: 2.5-fold higher) in a single subject. Coadministration of atazanavir and voriconazole may be feasible in selected HIV-positive patients; therapeutic drug monitoring and CYP2C19 genotyping may optimize exposure of both drugs.