A Gaedigk

..Allelic variants of cytochrome P450 CYP2D6 (CYP2D6), such as gene deletion, duplication, multiplication and conversion, contribute to the wide range of CYP2D6 activity. Novel gene arrangements were discovered and characterized...

..Due to premature termination codons, none encodes functional protein. The mechanisms leading to variable amounts of immunoreactive protein and distinct pre- and postnatal CYP2J2 protein patterns warrant further investigation...

..14408G/G that causes a premature stop codon in any splice variants that contain the 57bp intron 6 insertion. Therefore, no evidence for functional CYP2D7 transcripts was observed in Asian, Caucasian or African American individuals...

..This study aimed at characterising the CYP2D6 gene locus in Coloured subjects and predict their phenotype status...

..Quantitative assays to assess gene copy number are therefore becoming an integral part of accurate genotype assessment and phenotype prediction...

..Given a combined frequency of between 0.5 and 3% in African Americans and Asians, genotyping for CYP2D6*36 should improve the accuracy of genotype-based phenotype prediction in these populations...

..The AS tool warrants further prospective evaluation for CYP2D6 substrates and in additional ethnic populations...

..Different platforms exist for copy number variation (CNV) detection; however, there are no gold standards. Robust methods are required that address specific challenges to accurately determine gene CNVs in complex gene loci...

..We aimed to resolve the CYP2D6 31 no-calls, determine the allele haplotype, and corroborate that CYP2D6 31 is associated with a poor metabolizer phenotype...

..The goal of the study was to resolve this issue by characterizing the CYP2D6 gene locus in these patients...

..Affected individuals may not only exhibit resistance to quinone-based cancer therapy because of a decreased production of cytotoxic drug metabolites, but may also be more susceptible to toxicities associated with toxicants...

..For all individuals, the correct phenotype has been predicted. Discordant phenotype assignment occurred in only two individuals which subsequently was attributed to CYP2D6 inhibition by concomitant drug therapy...

..Therefore, these alleles may be extremely rare or absent, and unless other novel polymorphisms exist in this Inuit group one would not anticipate any CYP2C9 poor metabolizer subjects among this population...

..Accurate identification of gene duplication events is essential to avoid false-positive ultrarapid metabolism assignments and thus, overestimation of predicted activity and increased risk for unwanted adverse events...

..Although CYP2D6 has been studied extensively in different population groups, relatively little is known for black Americans...

..The rationale for this study was to resolve the discordance and to describe the novel non-functional allelic variant of CYP2D6 and its frequency in populations of different ethnic backgrounds...

..CYP2D6(*)45 and (*)46 have a combined frequency of 4% and can be identified by a common SNP. Carriers are predicted to exhibit an extensive or intermediate CYP2D6 phenotype...

..In contrast, DM N-demethylation developed significantly more slowly over the first year of life. Genotype and the temporal acquisition of drug biotransformation are critical determinants of a drug response in infants...

..tonsurans from other dermatophytes. Of the 92 isolates evaluated, this genotyping scheme distinguished 12 distinct strains, providing evidence of genetic heterogeneity in T. tonsurans...

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..The pharmacokinetic profile of oral and intravenous pantoprazole was similar in children ages 2 to 16 years. The doses used here were safe and well tolerated in this population...

..1. These data indicate that CYP2D6.17 exhibits reduced metabolic activity toward all three commonly used CYP2D6 substrates, although specific effects on substrate affinity and turnover demonstrate some substrate dependence...

..Although further development is required, these studies suggest that the [(13)C]-DM breath test offers promise as a rapid, minimally invasive phenotyping assay for CYP2D6 activity...

..This communication details mixed Trichophyton tonsurans infections and highlights the need to confirm the presence of multiple strains in a clinical single isolate by use of a multilocus approach...

..This investigation was designed to gain insight into the natural course of T. tonsurans infection...

..To extend the genotyping analysis of the CYP2D6 gene and further explain variability of CYP2D6 activity in Mexican Americans by genetic factors...

..2-fold (8.07 +/- 2.87, range 2.41 to 14.9 nmol/min/mg). Observed variability in CYP3A7 activity was not related to CYP3A7*2, and alternative regulatory mechanisms require further investigation...

..0001) and the apparent elimination rate constant (K(el); p = 0.0012); no significant genotype-phenotype relationships were observed for omeprazole...

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..The purpose of this study was to characterize the variability of APAP sulfation in a panel of human fetal livers and to identify the sulfotransferases (SULT) isoform(s) responsible for catalyzing that activity...

..Altered biotransformation of drugs in this patient population is likely enzyme- and isoform-specific and thus is apparent for only selected compounds that are substrates for enzymes other than CYP1A2, NAT-2, XO, and CYP2D6...

..To assess the correlation between plasma concentrations of four commonly administered selective serotonin reuptake inhibitors (SSRIs) and the magnitude of cytochrome P450 (CYP) 2D6 inhibition...

..The Cooperstown 5+1 cocktail may be used to simultaneously assess the activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A, NAT2, and XO...

..LSS using S-warfarin concentrations is an efficient and accurate technique to evaluate S-warfarin AUC(0- infinity ) when using warfarin as a CYP2C9 probe drug...

..5%, interquartile range = 14.8%-23.5%). Weight-based single doses of omeprazole for CYP2C19 phenotyping did not exhibit dose dependency. Therefore, a weight-based approach may improve the quantitation of omeprazole/metabolites...

..This triphasic oral contraceptive may have a clinically significant effect on the activity of some drug-metabolizing enzymes...

..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...

..We investigated whether metoprolol plasma concentrations, CYP2D6 polymorphisms, or genotype-derived phenotype was associated with adverse effects or efficacy in patients with hypertension...

..A gene-dose effect was observed. In addition, variations in endogenous sex steroid concentrations throughout the menstrual cycle did not influence CYP2C19 activity...

..Certain gastrointestinal and behavioral activation events (aggressive reaction and nervousness) were reported more frequently in the youngest age group...

..Options to reduce this risk include discontinuing codeine after 2 to 3 days of use and being aware of symptoms of potential opioid toxicity in both mothers and newborns...

..LPV/RTV may increase PHT clearance via CYP2C9 induction. Management should be individualized to each patient; dosage or medication adjustments may be necessary...

..Maribavir was safe and well tolerated. Taste disturbance was the most frequently reported adverse event. These results will further guide evaluation of the drug interaction potential and clinical development of maribavir...

..This knockout mouse model should be helpful in delineating the role that variation in acetylating enzymes plays in mediating interindividual differences in susceptibility to arylamine-induced chemical toxicity and/or carcinogenesis...