J S Leeder

Summary

Affiliation: Children's Mercy Hospital
Country: USA

Publications

  1. pmc Global tests of P-values for multifactor dimensionality reduction models in selection of optimal number of target genes
    Hongying Dai
    Department of Medical Research, Children s Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA
    BioData Min 5:3. 2012
  2. pmc Risk score modeling of multiple gene to gene interactions using aggregated-multifactor dimensionality reduction
    Hongying Dai
    Research Development and Clinical Investigation, Children s Mercy Hospital, Kansas City, MO, 64108, USA
    BioData Min 6:1. 2013
  3. doi request reprint Interpreting pharmacogenetic data in the developing neonate: the challenge of hitting a moving target
    J S Leeder
    Department of Pediatrics, University of Missouri Kansas City School of Medicine, Kansas City, Missouri, USA
    Clin Pharmacol Ther 92:434-6. 2012
  4. pmc Expression analysis of asthma candidate genes during human and murine lung development
    Erik Melen
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Respir Res 12:86. 2011
  5. pmc Platform dependence of inference on gene-wise and gene-set involvement in human lung development
    Rose Du
    Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
    BMC Bioinformatics 10:189. 2009
  6. pmc Genome-wide prediction, display and refinement of binding sites with information theory-based models
    Sashidhar Gadiraju
    Laboratory of Human Molecular Genetics, Children s Mercy Hospital and Clinics, School of Medicine, and School of Interdisciplinary Computer Science and Engineering University of Missouri Kansas City, Kansas City, MO 64108 USA
    BMC Bioinformatics 4:38. 2003
  7. ncbi request reprint Variability of CYP3A7 expression in human fetal liver
    J Steven Leeder
    Section of Developmental Pharmacology and Experimental Therapeutics, Children s Mercy Hospital and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
    J Pharmacol Exp Ther 314:626-35. 2005
  8. doi request reprint Understanding the relative roles of pharmacogenetics and ontogeny in pediatric drug development and regulatory science
    J Steven Leeder
    Division of Clinical Pharmacology and Medical Toxicology, Department of Pediatrics, Children s Mercy Hospitals and Clinics, School of Medicine, University of Missouri Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA
    J Clin Pharmacol 50:1377-87. 2010
  9. doi request reprint Developmental pharmacogenetics: a general paradigm for application to neonatal pharmacology and toxicology
    J S Leeder
    Division of Clinical Pharmacology and Medical Toxicology, Department of Pediatrics, Children s Mercy Hospitals and Clinics and School of Medicine, University of Missouri Kansas City, Kansas City, Missouri, USA
    Clin Pharmacol Ther 86:678-82. 2009
  10. ncbi request reprint Developmental and pediatric pharmacogenomics
    J Steven Leeder
    Section of Developmental Pharmacology and Experimental Therapeutics, Division of Pediatric Pharmacology and Medical Toxicology, Children s Mercy Hospital and Clinics, Kansas City, MO, USA
    Pharmacogenomics 4:331-41. 2003

Collaborators

Detail Information

Publications70

  1. pmc Global tests of P-values for multifactor dimensionality reduction models in selection of optimal number of target genes
    Hongying Dai
    Department of Medical Research, Children s Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA
    BioData Min 5:3. 2012
    ..abstract:..
  2. pmc Risk score modeling of multiple gene to gene interactions using aggregated-multifactor dimensionality reduction
    Hongying Dai
    Research Development and Clinical Investigation, Children s Mercy Hospital, Kansas City, MO, 64108, USA
    BioData Min 6:1. 2013
    ..abstract:..
  3. doi request reprint Interpreting pharmacogenetic data in the developing neonate: the challenge of hitting a moving target
    J S Leeder
    Department of Pediatrics, University of Missouri Kansas City School of Medicine, Kansas City, Missouri, USA
    Clin Pharmacol Ther 92:434-6. 2012
    ....
  4. pmc Expression analysis of asthma candidate genes during human and murine lung development
    Erik Melen
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Respir Res 12:86. 2011
    ..Little is known about the role of most asthma susceptibility genes during human lung development. Genetic determinants for normal lung development are not only important early in life, but also for later lung function...
  5. pmc Platform dependence of inference on gene-wise and gene-set involvement in human lung development
    Rose Du
    Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
    BMC Bioinformatics 10:189. 2009
    ..0 and the Illumina HumanRef-8 v2 Expression Bead Chips, for comparability in a biological system in which changes may be subtle, namely fetal lung tissue as a function of gestational age...
  6. pmc Genome-wide prediction, display and refinement of binding sites with information theory-based models
    Sashidhar Gadiraju
    Laboratory of Human Molecular Genetics, Children s Mercy Hospital and Clinics, School of Medicine, and School of Interdisciplinary Computer Science and Engineering University of Missouri Kansas City, Kansas City, MO 64108 USA
    BMC Bioinformatics 4:38. 2003
    ..The software can then be used to predict novel sites by rescanning the genome with the refined matrices...
  7. ncbi request reprint Variability of CYP3A7 expression in human fetal liver
    J Steven Leeder
    Section of Developmental Pharmacology and Experimental Therapeutics, Children s Mercy Hospital and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
    J Pharmacol Exp Ther 314:626-35. 2005
    ..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...
  8. doi request reprint Understanding the relative roles of pharmacogenetics and ontogeny in pediatric drug development and regulatory science
    J Steven Leeder
    Division of Clinical Pharmacology and Medical Toxicology, Department of Pediatrics, Children s Mercy Hospitals and Clinics, School of Medicine, University of Missouri Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA
    J Clin Pharmacol 50:1377-87. 2010
    ..The results of the analysis can be used to aid in the design of studies to yield maximally informative data in pediatric populations of different ages and developmental stages and thereby improve the efficiency of study design...
  9. doi request reprint Developmental pharmacogenetics: a general paradigm for application to neonatal pharmacology and toxicology
    J S Leeder
    Division of Clinical Pharmacology and Medical Toxicology, Department of Pediatrics, Children s Mercy Hospitals and Clinics and School of Medicine, University of Missouri Kansas City, Kansas City, Missouri, USA
    Clin Pharmacol Ther 86:678-82. 2009
    ..The challenge is to identify the specific factors--genetic and nongenetic--that contribute to increased risk...
  10. ncbi request reprint Developmental and pediatric pharmacogenomics
    J Steven Leeder
    Section of Developmental Pharmacology and Experimental Therapeutics, Division of Pediatric Pharmacology and Medical Toxicology, Children s Mercy Hospital and Clinics, Kansas City, MO, USA
    Pharmacogenomics 4:331-41. 2003
    ..Thus, there is considerable potential for large-scale pharmacogenomic technologies to impact the development and utilization of new therapeutic strategies in children...
  11. ncbi request reprint Application of pharmacogenomic strategies to the study of drug-induced birth defects
    J S Leeder
    Department of Pediatrics, Section of Developmental Pharmacology and Experimental Therapeutics, Children s Mercy Hospitals and Clinics, Kansas City, Missouri, USA
    Clin Pharmacol Ther 81:595-9. 2007
    ..Although the etiology and determinants of individual susceptibility are largely unknown for most congenital malformations, pharmacogenomic analyses offer promise for the future...
  12. ncbi request reprint Evaluation of a [13C]-dextromethorphan breath test to assess CYP2D6 phenotype
    J Steven Leeder
    Section of Developmental Pharmacology and Experimental Therapeutics, Department of Pediatrics, Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
    J Clin Pharmacol 48:1041-51. 2008
    ..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...
  13. ncbi request reprint The challenges of delivering pharmacogenomics into clinical pediatrics
    J S Leeder
    Section of Developmental Pharmacology and Experimental Therapeutics, Division of Pediatric Pharmacology and Medical Toxicology, Children s Mercy Hospital and Clinics, Kansas City, MO 64108, USA
    Pharmacogenomics J 2:141-3. 2002
  14. ncbi request reprint Pharmacogenetics and pharmacogenomics
    J S Leeder
    Section of Developmental Pharmacology and Experimental Therapeutics, Division of Clinical Pharmacology and Toxicology, Children s Mercy Hospital and Clinics, University of Kansas Medical Center, Kansas City, Kansas, USA
    Pediatr Clin North Am 48:765-81. 2001
    ....
  15. ncbi request reprint Translating pharmacogenetics and pharmacogenomics into drug development for clinical pediatrics and beyond
    J Steven Leeder
    Section of Developmental Pharmacology and Experimental Therapeutics, Children s Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA
    Drug Discov Today 9:567-73. 2004
    ..The lack of pharmacogenetic and pharmacogenomic investigations in children and the potential to impact on all age groups provides a considerable incentive to invest in this area of research...
  16. doi request reprint Personalized medicine: reality and reality checks
    J Steven Leeder
    Division of Clinical Pharmacology and MedicalToxicology, Children s Mercy Hospitals and Clinics, 2401 Gillham Rd, Kansas City, MO 64108, USA
    Ann Pharmacother 43:963-6. 2009
    ..The reality is that personalized medicine is upon us; open discourse and periodic reality checks will be necessary as we confront it...
  17. ncbi request reprint Non-monooxygenase cytochromes P450 as potential human autoantigens in anticonvulsant hypersensitivity reactions
    J S Leeder
    Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada
    Pharmacogenetics 8:211-25. 1998
    ....
  18. ncbi request reprint NAD(P)H:quinone oxidoreductase: polymorphisms and allele frequencies in Caucasian, Chinese and Canadian Native Indian and Inuit populations
    A Gaedigk
    Section of Pediatric Clinical Pharmacology and Experimental Therapeutics, The Children s Mercy Hospital, Kansas City, Missouri 64108, USA
    Pharmacogenetics 8:305-13. 1998
    ..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...
  19. ncbi request reprint The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype
    A Gaedigk
    Section of Developmental Pharmacology and Experimental Therapeutics, Children s Mercy Hospital and Clinics, Kansas City, Missouri, USA
    Clin Pharmacol Ther 83:234-42. 2008
    ..The AS tool warrants further prospective evaluation for CYP2D6 substrates and in additional ethnic populations...
  20. ncbi request reprint Ontogeny of dextromethorphan O- and N-demethylation in the first year of life
    M J Blake
    Division of Pediatric Pharmacology and Medical Toxicology, Department of Pediatrics, Children s Mercy Hospitals and Clinics, Kansas City, Missouri, USA
    Clin Pharmacol Ther 81:510-6. 2007
    ..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...
  21. ncbi request reprint Investigation of terbinafine as a CYP2D6 inhibitor in vivo
    S M Abdel-Rahman
    Children s Mercy Hospital, and the Department of Pediatrics, Pharmacy Practice, Pharmacology, and the Pharmaceutical Sciences, University of Missouri Kansas City, 64108, USA
    Clin Pharmacol Ther 65:465-72. 1999
    ..This prospective open-label study was designed to confirm our previous finding that terbinafine may inhibit CYP2D6...
  22. ncbi request reprint Identification and characterization of CYP2D6*56B, an allele associated with the poor metabolizer phenotype
    A Gaedigk
    Section of Developmental Pharmacology and Experimental Therapeutics, Children s Mercy Hospital and Clinics, Kansas City, Missouri, USA
    Clin Pharmacol Ther 81:817-20. 2007
    ..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...
  23. ncbi request reprint Cytochrome P450 Involvement in the biotransformation of cisapride and racemic norcisapride in vitro: differential activity of individual human CYP3A isoforms
    R E Pearce
    Division of Pediatric Clinical Pharmacology and Medical Toxicology, Children s Mercy Hospital, Kansas City, Missouri 64108, USA
    Drug Metab Dispos 29:1548-54. 2001
    ..g., ontogeny of drug-metabolizing enzymes, inhibition, and induction) should be clinically unimportant due to the apparent lack of dependence on cytochromes P450 for elimination...
  24. ncbi request reprint Potent inhibition of cytochrome P-450 2D6-mediated dextromethorphan O-demethylation by terbinafine
    S M Abdel-Rahman
    Section of Pediatric Clinical Pharmacology and Experimental Therapeutics, The Children s Mercy Hospital, Kansas City, Missouri 64108, USA
    Drug Metab Dispos 27:770-5. 1999
    ..This agent needs to be evaluated in vivo to determine the impact of CYP2D6 inhibition by terbinafine on the metabolism of concomitantly administered CYP2D6 substrates...
  25. ncbi request reprint Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations
    A Gaedigk
    Division of Pediatric Clinical Pharmacology and Toxicology, The Children s Mercy Hospital and Clinics, Kansas City, MO 64108, USA
    Can J Physiol Pharmacol 79:841-7. 2001
    ..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...
  26. doi request reprint Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study
    P Madadi
    Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada
    Clin Pharmacol Ther 85:31-5. 2009
    ..Breastfed infants of mothers who are CYP2D6 UMs combined with the UGT2B7*2/*2 are at increased risk of potentially life-threatening CNS depression...
  27. ncbi request reprint Concordance between tramadol and dextromethorphan parent/metabolite ratios: the influence of CYP2D6 and non-CYP2D6 pathways on biotransformation
    S M Abdel-Rahman
    Department of Pediatrics, University of Missouri Kansas City, USA
    J Clin Pharmacol 42:24-9. 2002
    ....
  28. ncbi request reprint Development and refinement of pregnane X receptor (PXR) DNA binding site model using information theory: insights into PXR-mediated gene regulation
    Carrie A Vyhlidal
    Section of Developmental Pharmacology and Experimental Therapeutics, Division of Pediatric Clinical Pharmacology and Medical Toxicology and Laboratory of Human Molecular Genetics, Children s Mercy Hospital and Clinics, Kansas City, Missouri 64108, USA
    J Biol Chem 279:46779-86. 2004
    ..69 bits at -7872) and was validated by binding studies and reporter assays as a PXR responsive element. This suggests that the PXR-mediated response extends beyond genes involved in drug biotransformation and transport...
  29. ncbi request reprint Comparison of various urine collection intervals for caffeine and dextromethorphan phenotyping in children
    Mary Jayne Kennedy
    Division of Pediatric Clinical Pharmacology, The Children s Mercy Hospitals and Clinics, Kansas City, MO, USA
    J Clin Pharmacol 44:708-14. 2004
    ..Longer collection periods may be required, however, in younger children or CYP2D6 poor metabolizers...
  30. ncbi request reprint Characterization of cytochrome P450 2D6.1 (CYP2D6.1), CYP2D6.2, and CYP2D6.17 activities toward model CYP2D6 substrates dextromethorphan, bufuralol, and debrisoquine
    Kenda A Marcucci
    Section of Developmental Pharmacology and Experimental Therapeutics, Division of Pediatric Clinical Pharmacology and Toxicology, Children s Mercy Hospital and Clinics, Kansas City, Missouri 64108, USA
    Drug Metab Dispos 30:595-601. 2002
    ..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...
  31. ncbi request reprint Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data
    A Gaedigk
    Section of Pediatric Clinical Pharmacology and Experimental Therapeutics, The Children s Mercy Hospital, and University of Missouri Kansas City, 64108, USA
    Pharmacogenetics 9:669-82. 1999
    ..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...
  32. doi request reprint The effect of genotype on methotrexate polyglutamate variability in juvenile idiopathic arthritis and association with drug response
    Mara L Becker
    Children s Mercy Hospitals and Clinics, Kansas City, Missouri 64108, USA
    Arthritis Rheum 63:276-85. 2011
    ..Therefore, this study was aimed at investigating the genetic predictors of MTXGlu variability and associations between MTXGlu and drug response in JIA...
  33. pmc Selective Toll--like receptor expression in human fetal lung
    Joshua E Petrikin
    Department of Pediatrics, University of Missouri Kansas City School of Medicine, Kansas City, Missouri 64108, USA
    Pediatr Res 68:335-8. 2010
    ..The best-fit curve predicts a 6.1-fold increase from 60 to 130 d. We conclude that TLR2 is developmentally expressed from the early pseudoglandular stage of lung development to the canalicular stage...
  34. ncbi request reprint A comparative study on computational two-block motif detection: algorithms and applications
    Chengpeng Bi
    Bioinformatics and Intelligent Computing, Division of Clinical Pharmacology and Toxicology, Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, Missouri 64108, USA
    Mol Pharm 5:3-16. 2008
    ..We demonstrate how to use this suite of methods and apply them to human nuclear receptor response elements (i.e., protein binding sites of several relevant nuclear receptors, HNF4alpha, CAR/RXR, and PXR/RXR)...
  35. pmc Pathways of carbamazepine bioactivation in vitro. III. The role of human cytochrome P450 enzymes in the formation of 2,3-dihydroxycarbamazepine
    Robin E Pearce
    Section of Developmental Pharmacology and Experimental Therapeutics, Division of Pediatric Pharmacology and Medical Toxicology, Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
    Drug Metab Dispos 36:1637-49. 2008
    ....
  36. ncbi request reprint UGT2B17 and SULT1A1 gene copy number variation (CNV) detection by LabChip microfluidic technology
    Andrea Gaedigk
    Section of Developmental Pharmacology and Experimental Therapeutics, The Children s Mercy Hospital and Clinics, Kansas City, MO 64108, USA
    Clin Chem Lab Med 48:627-33. 2010
    ..Quantitative assays to assess gene copy number are therefore becoming an integral part of accurate genotype assessment and phenotype prediction...
  37. ncbi request reprint Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations
    Mara L Becker
    Children s Mercy Hospital, Kansas City, Missouri, USA
    Arthritis Rheum 62:1803-12. 2010
    ..The present study was undertaken to measure intracellular MTXGlu concentrations in a cohort of patients with juvenile idiopathic arthritis (JIA) to determine the predictors of MTXGlu variability in these patients...
  38. doi request reprint CYP2D7-2D6 hybrid tandems: identification of novel CYP2D6 duplication arrangements and implications for phenotype prediction
    Andrea Gaedigk
    Section of Developmental Pharmacology and Experimental Therapeutics, The Children s Mercy Hospital and Clinics, 2401 Gillham Road, Kansas City, MO 62108, USA
    Pharmacogenomics 11:43-53. 2010
    ..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...
  39. doi request reprint Divergence among an international population of Trichophyton tonsurans isolates
    Susan M Abdel-Rahman
    Division of Clinical Pharmacology and Medical Toxicology, Children s Mercy Hospital, 2401 Gillham Road, Suite 0411, Kansas City, MO 64108, USA
    Mycopathologia 169:1-13. 2010
    ..The degree of genetic variation observed in this study coupled with the geographic localization would support the argument for allopatric divergence within this species...
  40. pmc Identifying genomic and developmental causes of adverse drug reactions in children
    Mara L Becker
    Children s Mercy Hospitals and Clinics, Division of Clinical Pharmacology, 2401 Gillham Road, Kansas City, MO 64110, USA
    Pharmacogenomics 11:1591-602. 2010
    ....
  41. ncbi request reprint Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants
    Michael J Blake
    Department of Pediatrics, University of Missouri Kansas City, School of Medicine and the Division of Pediatric Pharmacology and Medical Toxicology, Children s Mercy Hospitals and Clinics, Kansas City, Missouri 64108, USA
    Pediatr Res 60:717-23. 2006
    ..Dietary modification of CYP activity may modulate drug biotransformation and thus alter systemic exposure to xenobiotics from a very early age...
  42. pmc Variability of CYP2J2 expression in human fetal tissues
    Andrea Gaedigk
    Children s Mercy Hospital, Division of Clinical Pharmacology, 2401 Gillham Rd, Kansas City, MO 64108, USA
    J Pharmacol Exp Ther 319:523-32. 2006
    ..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...
  43. ncbi request reprint Pathways of carbamazepine bioactivation in vitro: II. The role of human cytochrome P450 enzymes in the formation of 2-hydroxyiminostilbene
    Robin E Pearce
    Section of Developmental Pharmacology and Experimental Therapeutics, Division of Pediatric Pharmacology and Medical Toxicology, Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, Missouri 64108, USA
    Drug Metab Dispos 33:1819-26. 2005
    ....
  44. ncbi request reprint CYP2D7 splice variants in human liver and brain: does CYP2D7 encode functional protein?
    Andrea Gaedigk
    Division of Clinical Pharmacology and Experimental Therapeutics, The Children s Mercy Hospital and Clinics, Kansas City, MO, USA
    Biochem Biophys Res Commun 336:1241-50. 2005
    ..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...
  45. ncbi request reprint Nuclear receptor expression in fetal and pediatric liver: correlation with CYP3A expression
    Carrie A Vyhlidal
    Section of Developmental Pharmacology and Experimental Therapeutics, Children s Mercy Hospital and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
    Drug Metab Dispos 34:131-7. 2006
    ..610 and 0.723 for PXR and CAR, respectively). In conclusion, nuclear receptor mRNA expression demonstrates considerable interindividual variability in human fetal and pediatric liver and is significantly correlated with CYP3A expression...
  46. ncbi request reprint Information theory-based analysis of CYP2C19, CYP2D6 and CYP3A5 splicing mutations
    Peter K Rogan
    Laboratory of Human Molecular Genetics, Children s Mercy Hospital and Clinics, Kansas City, Missouri 64108, USA
    Pharmacogenetics 13:207-18. 2003
    ....
  47. pmc Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans
    A Gaedigk
    Division of Clinical Pharmacology and Experimental Therapeutics, Children s Mercy Hospital and Clinics, Kansas City, MO 64108, USA
    Pharmacogenomics J 5:173-82. 2005
    ..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...
  48. ncbi request reprint Developmental pharmacology--drug disposition, action, and therapy in infants and children
    Gregory L Kearns
    Department of Pediatrics, University of Missouri at Kansas City, Kansas City, MO, USA
    N Engl J Med 349:1157-67. 2003
  49. ncbi request reprint CYP2D6*36 gene arrangements within the cyp2d6 locus: association of CYP2D6*36 with poor metabolizer status
    Andrea Gaedigk
    Section of Developmental Pharmacology and Experimental Therapeutics, Children s Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA
    Drug Metab Dispos 34:563-9. 2006
    ..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...
  50. ncbi request reprint CYP2D6 poor metabolizer status can be ruled out by a single genotyping assay for the -1584G promoter polymorphism
    Andrea Gaedigk
    Division of Developmental Pharmacology and Medical Toxicology, The Children s Mercy Hospital and Clinics, Kansas City, MO 64108, USA
    Clin Chem 49:1008-11. 2003
  51. ncbi request reprint Pathways of carbamazepine bioactivation in vitro I. Characterization of human cytochromes P450 responsible for the formation of 2- and 3-hydroxylated metabolites
    Robin E Pearce
    Section of Developmental Pharmacology and Experimental Therapeutics, Division of Pediatric Clinical Pharmacology and Medical Toxicology, Children s Mercy Hospitals and Clinics, Kansas City, Missouri 64108, USA
    Drug Metab Dispos 30:1170-9. 2002
    ..These results suggest that CYP2B6 and CYP3A4 are largely responsible for the formation of 3-hyrdoxycarbamazepine, whereas multiple P450s (CYP1A2, 2A6, 2B6, 2E1, and 3A4) contributed to 2-hydroxycarbamazepine formation...
  52. ncbi request reprint Unique CYP2D6 activity distribution and genotype-phenotype discordance in black Americans
    Andrea Gaedigk
    Division of Pediatric Clinical Pharmacology and Medical Toxicology, Children s Mercy Hospital and Clinics, Kansas City, MO 64108 USA
    Clin Pharmacol Ther 72:76-89. 2002
    ..Although CYP2D6 has been studied extensively in different population groups, relatively little is known for black Americans...
  53. pmc Impact of the CYP2C19*17 allele on the pharmacokinetics of omeprazole and pantoprazole in children: evidence for a differential effect
    Gregory L Kearns
    Director, Pharmacogenetics Core Laboratory, Division of Clinical Pharmacology and Medical Toxicology, Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
    Drug Metab Dispos 38:894-7. 2010
    ..0001) and the apparent elimination rate constant (K(el); p = 0.0012); no significant genotype-phenotype relationships were observed for omeprazole...
  54. ncbi request reprint Cisapride: a potential model substrate to assess cytochrome P4503A4 activity in vivo
    Jennifer A Lowry
    Division of Pediatric Clinical Pharmacology and Medical Toxicology, Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
    Clin Pharmacol Ther 73:209-22. 2003
    ..Cisapride was compared with midazolam in vivo to determine its potential applicability as a cytochrome P450 (CYP) 3A4 "probe." As well, we evaluated whether cisapride was transported by P-glycoprotein...
  55. ncbi request reprint Ontogeny of drug metabolizing enzymes in the neonate
    Michael J Blake
    Department of Pediatrics, University of Missouri Kansas City, Division of Pediatric Pharmacology and Medical Toxicology, The Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
    Semin Fetal Neonatal Med 10:123-38. 2005
    ....
  56. ncbi request reprint Biotransformation of fluticasone: in vitro characterization
    Robin E Pearce
    Division of Pediatric Clinical Pharmacology and Medical Toxicology, Department of Pediatrics, Children s Mercy Hospitals and Clinics, Kansas City, MO 64108, USA
    Drug Metab Dispos 34:1035-40. 2006
    ..These results suggest that at pharmacologically relevant concentrations, biotransformation of FTP to M1 is mediated predominantly by CYP3A enzymes in the liver...
  57. ncbi request reprint A method for meta-analysis of epidemiological studies
    T R Einarson
    Department of Pediatrics, Hospital for Sick Children, Toronto, ON
    Drug Intell Clin Pharm 22:813-24. 1988
    ..62-1.45. For case-control studies, the summary odds ratio was 1.27 with a 95 percent confidence interval of 0.83-1.94. The corresponding chi-square values were not statistically significant at the p = 0.05 level...
  58. pmc Effects of valproic acid on organic acid metabolism in children: a metabolic profiling study
    K E Price
    Division of Clinical Pharmacology and Medical Toxicology, Department of Pediatrics, Children s Mercy Hospitals and Clinics, Kansas City, Missouri, USA
    Clin Pharmacol Ther 89:867-74. 2011
    ..The data suggest that more detailed metabolomic analysis may provide novel insights into biological mechanisms and predictive biomarkers for children at highest risk for serious toxicity...
  59. doi request reprint Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects
    Araba A Adjei
    Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Birth Defects Res A Clin Mol Teratol 82:155-65. 2008
    ..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...
  60. ncbi request reprint Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension
    Issam Zineh
    Department of Pharmacy Practice, University of Florida, Gainesville, FL 32610, USA
    Clin Pharmacol Ther 76:536-44. 2004
    ..We investigated whether metoprolol plasma concentrations, CYP2D6 polymorphisms, or genotype-derived phenotype was associated with adverse effects or efficacy in patients with hypertension...
  61. ncbi request reprint Cytochrome P450 pharmacogenetics and anaesthesia
    Christian Seefelder
    Paediatr Anaesth 12:810-1. 2002
  62. ncbi request reprint Comments on Hoskins et al. [(2005) drug metab dispos 33:1564-1565]
    Andrea Gaedigk
    Drug Metab Dispos 34:504-5; author reply 506. 2006
  63. ncbi request reprint Limited association of the 2988g > a single nucleotide polymorphism with CYP2D641 in black subjects
    Andrea Gaedigk
    Clin Pharmacol Ther 77:228-30; author reply 230-1. 2005
  64. ncbi request reprint Effect of a triphasic oral contraceptive on drug-metabolizing enzyme activity as measured by the validated Cooperstown 5+1 cocktail
    Tatiana Shelepova
    Department of Medicine, Clinical Pharmacology Research Center, Bassett Healthcare, Cooperstown, New York, USA
    J Clin Pharmacol 45:1413-21. 2005
    ..This triphasic oral contraceptive may have a clinically significant effect on the activity of some drug-metabolizing enzymes...
  65. ncbi request reprint Discovery of a novel nonfunctional cytochrome P450 2D6 allele, CYP2D642, in African American subjects
    Andrea Gaedigk
    Clin Pharmacol Ther 73:575-6. 2003
  66. ncbi request reprint Bioactivation of clozapine by murine cardiac tissue in vivo and in vitro
    Dominic P Williams
    Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, United Kingdom
    Chem Res Toxicol 16:1359-64. 2003
    ..5 +/- 0.06%, respectively. These data indicate that clozapine undergoes bioactivation in the heart to a chemically reactive nitrenium metabolite that may be important in the pathogenesis of myocarditis and cardiomyopathy observed in man...
  67. ncbi request reprint Combined phenotypic assessment of cytochrome p450 1A2, 2C9, 2C19, 2D6, and 3A, N-acetyltransferase-2, and xanthine oxidase activities with the "Cooperstown 5+1 cocktail"
    Siwaporn Chainuvati
    Department of Medicine, Bassett Healthcare, Cooperstown, NY 13326, USA
    Clin Pharmacol Ther 74:437-47. 2003
    ..The Cooperstown 5+1 cocktail may be used to simultaneously assess the activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A, NAT2, and XO...
  68. pmc CYP3A4-Mediated carbamazepine (CBZ) metabolism: formation of a covalent CBZ-CYP3A4 adduct and alteration of the enzyme kinetic profile
    Ping Kang
    Department of Cellular and Molecular Pharmacology, Liver Center, University of California, San Francisco, 600 16th Street N572F, San Francisco, CA 94158 2280, USA
    Drug Metab Dispos 36:490-9. 2008
    ....
  69. ncbi request reprint Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder
    Robert L Findling
    Department of Psychiatry, Case Western Reserve University, University Hospitals of Cleveland, OH 44106 5080, USA
    Neuropsychopharmacology 31:1274-85. 2006
    ..Certain gastrointestinal and behavioral activation events (aggressive reaction and nervousness) were reported more frequently in the youngest age group...
  70. pmc Safety of codeine during breastfeeding: fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine
    Parvaz Madadi
    Can Fam Physician 53:33-5. 2007
    ..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...

Research Grants6

  1. PATHOGENESIS OF ANTICONVULSANT HYPERSENSITIVITY SYNDROME
    JAMES LEEDER; Fiscal Year: 2000
    ..It is anticipated that the basic experimental paradigm employed for these studies can also be applied to other idiosyncratic toxicities with suspected drug bioactivation and immune etiologies. ..
  2. PATHOGENESIS OF ANTICONVULSANT HYPERSENSITIVITY SYNDROME
    JAMES LEEDER; Fiscal Year: 2001
    ..It is anticipated that the basic experimental paradigm employed for these studies can also be applied to other idiosyncratic toxicities with suspected drug bioactivation and immune etiologies. ..
  3. PATHOGENESIS OF ANTICONVULSANT HYPERSENSITIVITY SYNDROME
    JAMES LEEDER; Fiscal Year: 2002
    ..It is anticipated that the basic experimental paradigm employed for these studies can also be applied to other idiosyncratic toxicities with suspected drug bioactivation and immune etiologies. ..
  4. PATHOGENESIS OF ANTICONVULSANT HYPERSENSITIVITY SYNDROME
    JAMES LEEDER; Fiscal Year: 2003
    ..It is anticipated that the basic experimental paradigm employed for these studies can also be applied to other idiosyncratic toxicities with suspected drug bioactivation and immune etiologies. ..
  5. Ontogeny of Drug Bioactivation and Idiosyncratic ADRs
    JAMES LEEDER; Fiscal Year: 2007
    ..abstract_text> ..
  6. Exogenous and Endogenous Biomarkers of CYP2D6 Variability in Pediatrics
    YVONNE SARAH LIN; Fiscal Year: 2010
    ..Ultimately, the goal of the research is to personalize the use of medications in children by selecting the appropriate dose of the correct medication for individual patients. ..