Julia Kirchheiner

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..A controlled prospective clinical trial with one arm receiving genotype-based dose adjustments and the other arm receiving therapy as usual will elucidate the benefit of pharmacogenomics-based individualization of certain drug therapies...

..However, routine application of pharmacogenetic dose adjustment in clinical practice requires prospective validation...

..Here we derived PPI dose equivalents based on a comprehensive assessment of dose-dependent effects on intragastric pH...

..We aimed to analyze whether these findings could be reproduced in a different sample of otherwise comparable inpatients with major depression...

..It is unknown how genetic polymorphisms affect formation of these diuretic, vasodilatory and anti-inflammatory eicosanoids, and whether the CYP2C8 substrate rosiglitazone inhibits their formation...

..6 (95% CI 0.8-3.2) and carriers of the 9/9 genotype had an OR of 6.0 (1.5-24.4) for no or poor response. Further studies are required to confirm this clinical association and to elucidate the underlying mechanisms...

..Therefore, tramadol may frequently cause adverse effects in southern European and Northern African populations with a high proportion of UMs...

..So far, transporter genotypes are not yet eligible for individual prediction of drug response...

..Thus, a more favorable tamoxifen treatment seems to be feasible through a priori genetic assessment of CYP2D6...

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..The purpose of this was to clarify the role of this polymorphism with regard to the pharmacokinetics and clinical effects of rosiglitazone...

..Here, we review the potential impact of an integrated approach, including the assessment of intermediate phenotypes for the effect of genetic polymorphism, the monitoring of therapy progress, and response prediction in depression...

..It might be good if physicians would know about the CYP2D6 duplication genotype of their patients before administering codeine...

..An exploratory analysis, extended to the whole brain, suggested the involvement of CYP2D6 in regions associated with alertness or serotonergic function. These findings support the hypothesis of a functional role of CYP2D6 in the brain...

..We explored the impact of these polymorphisms on glyburide pharmacokinetics and the effects on insulin and glucose concentrations...

..According to in vitro data, about 70% of nateglinide intrinsic clearance may be mediated by cytochrome P450 (CYP) 2C9 and a smaller fraction by CYP3A4 and CYP2D6...

..This indicates that both CYP2C enzymes contribute to the demethylation of desmethyltrimipramine and CYP2D6 to further metabolism...

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..We studied the effect of the CYP2D6 duplication genotype on doxepin pharmacokinetics and platelet serotonin uptake and concentrations...

..In humans, there are 2 variants of CYP2C9 with a high population frequency. We studied their impact on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2...

..The CYP2D6 polymorphism had a major impact on E-doxepin pharmacokinetics and CYP2D6 PMs might be at an elevated risk for adverse drug effects when treated with common recommended doses...

..We compared metoprolol pharmacokinetics and effects in UMs with extensive metabolizers (EMs) and with poor metabolizers (PM) as an additional reference group...

..It remains to be shown whether this is associated with greater efficacy or with an increased incidence and severity of adverse events...

..As a surrogate marker of diclofenac activity, the ex vivo formation of prostaglandin E2 and thromboxane B2, which reflects COX-2 and COX-1 activity, was measured...

..The consequences of CYP2C9 genetic polymorphisms on fluvastatin pharmacokinetics and on its efficacy have not been investigated in humans thus far...

..Lithium augmentation is a well-established strategy for overcoming treatment resistance. In this study, the 5-HTTLPR allele variant's effect on lithium augmentation was analyzed in antidepressant-nonresponsive patients...

..However, regarding phenprocoumon hydroxylation CYP2C9 genotypes had only marginal effects on S- and R-phenprocoumon total clearance in healthy volunteers...

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..We hypothesized that ultrarapid metabolizers (defined as carriers of the CYP2D6 gene duplication plus another functional allele) have a risk for therapeutic failure due to too low tissue concentrations...

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..The role of this allele should also be studied in other CYP2B6 substrates, including cyclophosphamide, halothane, mianserin, promethazine and propofol...

..04). CONCLUSIONS: CYP3A4 mRNA concentrations in blood cells were very low and did not reflect systemic drug clearance mediated by CYP3A enzymes. The CYP3A5 genetic polymorphism does not appear relevant for alprazolam kinetics...

..g. receptor) also depends on genetic factors. In some cases genetic tests can help distinguish between responders and non-responders of a specific drug treatment. The first pharmacogenetic tests are already on the market...

..We reassess the findings of an increased baseline perfusion in the amygdala and ventral prefrontal areas in healthy carriers of the risk genotype in a much larger sample than in previous studies...

..However, the effect of CYP2D6 genotype on steady state kinetics and on bioavailability has not been studied so far. In addition, we were interested in trimipramine pharmacokinetics in genetically defined ultra rapid metabolizers...

..The importance of MDR1 SNPs 2677G > T/A in exon 21 and 3435C > T in exon 26 for cancer susceptibility, however, has not yet been clearly defined...

..The pronounced differences in pharmacokinetics due to the amino acid variants did not significantly affect plasma insulin and glucose concentrations in healthy volunteers...

..This study investigates the association of the GSK3B -50T/C SNP and response to lithium augmentation in acutely depressed antidepressant nonresponders...

..The impact of the polymorphism on haloperidol pharmacokinetics, adverse events, and efficacy was prospectively evaluated under naturalistic conditions in 172 unselected psychiatric inpatients with acute psychotic symptoms...

..Sample preparation time and analysis time are both short and allow rapid analysis of large sample sets...

..In urine, Mor/Cod ratios were below one for all EMs and UMs during the first 12 h. Thus, CYP2D6 genotyping in general will not explain Mor/Cod ratios > 1 in plasma or urine, unless the time of drug intake is more than 24 h previous...

..In addition to antidepressive drugs, several drugs used in cancer therapy, beta-blockers, proton pump inhibitors, and opioid analgesics are metabolized by these enzymes...

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..This is a first attempt to apply the new pharmacogenetics to suggest dose-regimens that take the differences in drug metabolic capacity into account...

..Clinicians should be made aware of the differences reported in the literature regarding the symptomatology, severity and recognition of the adverse psychotropic drug effects found in men and women...

..9 to 14.2%. The achieved limits of quantitation (LOQ) of 10 ng/ml for each analyte allowed the determination of the pharmacokinetic parameters of the analytes after administration of 100 mg celecoxib...

..Despite their strong statistical support, all 3 signals emerged from heterogeneous case-control populations and lack replication in different settings...

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..The Gly972Arg polymorphism in the insulin receptor substrate-1 (IRS-1) has been shown to play a role in insulin signal transduction and therapeutic failure to sulphonylurea drugs...

..Although dysfunction of 5-HT neurotransmission has been implicated in a variety of neuropsychiatric conditions, the human TPH2 promoter has not been characterized in vitro...

..Especially for drugs with a narrow therapeutic index and a high risk for the development of adverse drug effects, genotyping could be helpful when choosing the right drug in the optimal dosage for individual patients...

..To review the literature on the use of atypical antipsychotics in anorexia nervosa of children and adolescents and to present three case reports on quetiapine treatment of this subgroup...

..Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research...

..However, therapeutically active doses of 500 mg bear the risk of hypoglycaemia, and a tolbutamide-derived parameter based on a single plasma or urine concentration reflecting CYP2C9 activity accurately is lacking...

..It therefore represents a very efficient and fast method, offering new perspectives for the application of pharmacogenetics in clinical medicine...

..This article presents specific clinical examples of such challenges and discusses how obstacles to implementation of pharmacogenomic testing can be addressed...

..We also assessed whether urinary excretion of N-desmethylmephenytoin (nirvanol) might be a useful CYP2B6 metric in in vivo studies...

..However, our current understanding of the role of CYP2C9 in biotransformation of endogenous signaling molecules and in drug toxicity is relatively meager...

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..CONCLUSIONS: Cigarette smoking does not affect CYP2C9 activity as evaluated using S-warfarin as a CYP2C9 probe. Fluvastatin is a weak inhibitor of CYP2C9 activity in both smokers and non-smokers...

..Here, we argue for the development of concise guidelines for implementation of PGx analyses in drug development and therapy...

..They highlight a novel mechanism of OATP1B1-based interaction that is mediated by transcription factor HNF1alpha...

..In this study, we analyzed the correlation between TPH2 polymorphisms and response to antidepressant drugs...