D A Flockhart

Summary

Affiliation: Indiana University
Country: USA

Publications

  1. pmc Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series
    Wenjie J Lu
    Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA
    J Med Case Reports 5:513. 2011
  2. pmc An integrated pharmacokinetics ontology and corpus for text mining
    Heng yi Wu
    Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University, Indianapolis, IN, USA
    BMC Bioinformatics 14:35. 2013
  3. pmc Comparison of changes in the lipid profile of postmenopausal women with early stage breast cancer treated with exemestane or letrozole
    Lauren Nicole Bell
    Division of Clinical Pharmacology, Wishard Memorial Hospital, WD Myers Bldg, W7123, 1001 West 10th St, Indianapolis, IN 46202, USA
    J Clin Pharmacol 52:1852-60. 2012
  4. doi request reprint Dietary restrictions and drug interactions with monoamine oxidase inhibitors: an update
    David A Flockhart
    Indiana Insitute for Personalized Medicine and Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    J Clin Psychiatry 73:17-24. 2012
  5. pmc CYP2D6 genotype and tamoxifen response
    James M Rae
    Breast Cancer Res 7:E6. 2005
  6. pmc A modulated empirical Bayes model for identifying topological and temporal estrogen receptor α regulatory networks in breast cancer
    Changyu Shen
    Center for Computational Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    BMC Syst Biol 5:67. 2011
  7. pmc Finding the right research question: quality science depends on quality careers
    D A Flockhart
    Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 84:427-9. 2008
  8. ncbi request reprint Implications of cytochrome P450 interactions when prescribing medication for hypertension
    David A Flockhart
    Division of Clinical Pharmacology, Indiana University School of Medicine, Wishard Hospital, OPW 320, 1001 W 10th St, Indianapolis, IN 46202, USA
    Arch Intern Med 162:405-12. 2002
  9. pmc Clinically available pharmacogenomics tests
    D A Flockhart
    Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 86:109-13. 2009
  10. pmc Plasma letrozole concentrations in postmenopausal women with breast cancer are associated with CYP2A6 genetic variants, body mass index, and age
    Z Desta
    Department of Medicine, Indiana University, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 90:693-700. 2011

Research Grants

  1. MECHANISMS OF CARDIOTOXICITY OF ANTIPSYCHOTIC DRUGS
    David Flockhart; Fiscal Year: 2001

Detail Information

Publications88

  1. pmc Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series
    Wenjie J Lu
    Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA
    J Med Case Reports 5:513. 2011
    ..abstract:..
  2. pmc An integrated pharmacokinetics ontology and corpus for text mining
    Heng yi Wu
    Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University, Indianapolis, IN, USA
    BMC Bioinformatics 14:35. 2013
    ....
  3. pmc Comparison of changes in the lipid profile of postmenopausal women with early stage breast cancer treated with exemestane or letrozole
    Lauren Nicole Bell
    Division of Clinical Pharmacology, Wishard Memorial Hospital, WD Myers Bldg, W7123, 1001 West 10th St, Indianapolis, IN 46202, USA
    J Clin Pharmacol 52:1852-60. 2012
    ..In conclusion, AI treatment and/or washout of tamoxifen induced detrimental changes in the lipid profile of postmenopausal women with breast cancer...
  4. doi request reprint Dietary restrictions and drug interactions with monoamine oxidase inhibitors: an update
    David A Flockhart
    Indiana Insitute for Personalized Medicine and Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    J Clin Psychiatry 73:17-24. 2012
    ....
  5. pmc CYP2D6 genotype and tamoxifen response
    James M Rae
    Breast Cancer Res 7:E6. 2005
  6. pmc A modulated empirical Bayes model for identifying topological and temporal estrogen receptor α regulatory networks in breast cancer
    Changyu Shen
    Center for Computational Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    BMC Syst Biol 5:67. 2011
    ..Dynamic gene expression changes have been shown to characterize the breast cancer cell response to estrogens, the every molecular mechanism of which is still not well understood...
  7. pmc Finding the right research question: quality science depends on quality careers
    D A Flockhart
    Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 84:427-9. 2008
    ..The project must synthesize the excitement and idealism of contributing to the well-being of humankind and the practical realities of an area of inquiry that is likely to lead to a successful career...
  8. ncbi request reprint Implications of cytochrome P450 interactions when prescribing medication for hypertension
    David A Flockhart
    Division of Clinical Pharmacology, Indiana University School of Medicine, Wishard Hospital, OPW 320, 1001 W 10th St, Indianapolis, IN 46202, USA
    Arch Intern Med 162:405-12. 2002
    ....
  9. pmc Clinically available pharmacogenomics tests
    D A Flockhart
    Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 86:109-13. 2009
    ..Lessons can be learned from examination of these tests, the evidence that has catalyzed their use, their value to prescribers, and their merit as tools for personalizing therapeutics...
  10. pmc Plasma letrozole concentrations in postmenopausal women with breast cancer are associated with CYP2A6 genetic variants, body mass index, and age
    Z Desta
    Department of Medicine, Indiana University, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 90:693-700. 2011
    ..CYP2A6 metabolic status, along with BMI and age, may serve as a biomarker of the efficacy of letrozole treatment or a predictor of adverse effects...
  11. ncbi request reprint Stereoselective metabolism of cisapride and enantiomer-enantiomer interaction in human cytochrome P450 enzymes: major role of CYP3A
    Z Desta
    Division of Clinical Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA
    J Pharmacol Exp Ther 298:508-20. 2001
    ....
  12. ncbi request reprint CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment
    Yan Jin
    Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    J Natl Cancer Inst 97:30-9. 2005
    ....
  13. ncbi request reprint CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes
    Jacqueline Ramirez
    University of Chicago, Department of Medicine, Section of Hematology Oncology, 5841 S Maryland Avenue, MC2115, Chicago, IL 60637, USA
    Drug Metab Dispos 32:930-6. 2004
    ..We conclude that normeperidine formation in human liver microsomes is mainly catalyzed by CYP2B6 and CYP3A4, with a minor contribution from CYP2C19...
  14. pmc Inhibition of cytochrome P450 (CYP450) isoforms by isoniazid: potent inhibition of CYP2C19 and CYP3A
    Z Desta
    Division of Clinical Pharmacology, Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA
    Antimicrob Agents Chemother 45:382-92. 2001
    ..These data provide a rational basis for understanding drug interaction with INH and predict that other drugs metabolized by these two enzymes may also interact...
  15. ncbi request reprint Interaction of cisapride with the human cytochrome P450 system: metabolism and inhibition studies
    Z Desta
    Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA
    Drug Metab Dispos 28:789-800. 2000
    ..Cisapride metabolism is likely to be subject to interindividual variability in CYP3A expression and to drug interactions involving this isoform...
  16. pmc Estrogen receptor genotypes, menopausal status, and the lipid effects of tamoxifen
    N I Ntukidem
    Department of Medicine, Indiana University, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 83:702-10. 2008
    ..002; gene-dose effect) and high-density lipoprotein (P=0.004; gene-dose effect). Our results suggest that estrogen receptor genotyping may be useful in predicting which women would benefit more from tamoxifen...
  17. ncbi request reprint Stereoselective determination of cisapride, a prokinetic agent, in human plasma by chiral high-performance liquid chromatography with ultraviolet detection: application to pharmacokinetic study
    Z Desta
    Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA
    J Chromatogr B Biomed Sci Appl 744:263-72. 2000
    ..The preliminary pharmacokinetic data obtained using the method we describe here provide evidence for the first time that cisapride exhibits stereoselective disposition...
  18. ncbi request reprint Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine
    Vered Stearns
    The Breast Cancer Program, Department of Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA
    J Natl Cancer Inst 95:1758-64. 2003
    ..In a prospective clinical trial, we tested the effects of coadministration of tamoxifen and the SSRI paroxetine, an inhibitor of CYP2D6, on tamoxifen metabolism...
  19. ncbi request reprint Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy poor and extensive metabolizers of cytochrome P450 2D6 (CYP2D6)
    Z Desta
    Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA
    Clin Pharmacol Ther 65:10-20. 1999
    ..In this study, we examined the effect of clarithromycin on pimozide pharmacokinetics and QT interval changes in a total of 12 healthy subjects (7 men and 5 women), documented as extensive metabolizers or poor metabolizers of CYP2D6...
  20. ncbi request reprint Olanzapine-induced rhabdomyolysis
    C J Rosebraugh
    Division of Clinical Pharmacology, Georgetown University Medical Center, Washington, DC 20007 2195, USA
    Ann Pharmacother 35:1020-3. 2001
    ..To report a possible case of olanzapine-induced rhabdomyolysis with concomitant lithium-induced pseudo-infarction electrocardiogram changes...
  21. pmc Induction of CYP2C19 and CYP3A activity following repeated administration of efavirenz in healthy volunteers
    V Michaud
    Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 91:475-82. 2012
    ..In conclusion, efavirenz enhances omeprazole metabolism in a nonstereoselective manner through induction of CYP3A and CYP2C19 activity...
  22. ncbi request reprint The star-allele nomenclature: retooling for translational genomics
    J D Robarge
    Division of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 82:244-8. 2007
    ..As genomics research expands, it is equally important that the system remain a valuable tool for the wider community of genetic researchers to exploit our ever-improving ability to catalog variability in the human genome...
  23. ncbi request reprint Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6
    M Desai
    Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Wishard Memorial Hospital, 1001 W 10th Street, Indianapolis, IN 46202 2879, USA
    Pharmacogenomics J 3:105-13. 2003
    ..Although the magnitude of the mean QT(c) prolongation on haloperidol relative to placebo is relatively small, it may assume significance in the presence of other risk factors for QT prolongation...
  24. pmc Stereoselective pharmacokinetics of cisapride in healthy volunteers and the effect of repeated administration of grapefruit juice
    Z Desta
    Division of Clinical Pharmacology, Georgetown University Medical Center, Washington DC 20007, USA
    Br J Clin Pharmacol 52:399-407. 2001
    ..To determine whether the pharmacokinetics of cisapride and its interaction with grapefruit juice are stereoselective...
  25. ncbi request reprint Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: implications for cyclophosphamide metabolism
    James M Rae
    Division of Clinical Pharmacology, Department of Medicine, Georgetown University Medical Center, Washington, DC, USA
    Drug Metab Dispos 30:525-30. 2002
    ..Furthermore, thioTEPA may prove to be a valuable new tool for the study of this important drug-metabolizing enzyme...
  26. pmc Inhibition of drug metabolizing cytochrome P450s by the aromatase inhibitor drug letrozole and its major oxidative metabolite 4,4'-methanol-bisbenzonitrile in vitro
    Seongwook Jeong
    Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Cancer Chemother Pharmacol 64:867-75. 2009
    ..To determine the inhibitory potency of letrozole and its main human metabolite, 4,4'-methanol-bisbenzonitrile, on the activities of eight cytochrome P450 (CYP) enzymes...
  27. ncbi request reprint Endoxifen, a secondary metabolite of tamoxifen, and 4-OH-tamoxifen induce similar changes in global gene expression patterns in MCF-7 breast cancer cells
    Young Chai Lim
    Division of Clinical Pharmacology, Indiana University School of Medicine, 1001 West 10th Street, WD Myers Bldg, W7123, Indianapolis, IN 46202, USA
    J Pharmacol Exp Ther 318:503-12. 2006
    ..We conclude that endoxifen and 4-OH-Tam have similar effects on global gene expression patterns in MCF-7 cells and that the majority of the affected genes are estrogen-regulated genes...
  28. ncbi request reprint Drug-drug interaction prediction: a Bayesian meta-analysis approach
    Lang Li
    Division of Biostatistics, Department of Medicine, Indiana University, IN, USA
    Stat Med 26:3700-21. 2007
    ..Sensitivity analysis is conducted to justify prior distribution selections...
  29. doi request reprint Composite functional genetic and comedication CYP2D6 activity score in predicting tamoxifen drug exposure among breast cancer patients
    Silvana Borges
    Division of Biostatistics Clinical Pharmacology, Indiana University, School of Medicine, 410 W 10th St, HITS 3000, Indianapolis, IN 46202 e mail
    J Clin Pharmacol 50:450-8. 2010
    ..However, endoxifen phenotypes still varied substantially, even with incorporation of CYD2D6 genotype and inhibiting factors, suggesting that other, as yet unidentified factors must be involved in tamoxifen activation...
  30. ncbi request reprint Predicting asparaginase-associated pancreatitis
    Holly M Knoderer
    Department of Pediatric Hematology Oncology, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Pediatr Blood Cancer 49:634-9. 2007
    ..There is no predictor of who will develop asparaginase-associated pancreatitis (AAP). To better define this population, we present a retrospective analysis regarding AAP and provide a review of the relevant literature...
  31. ncbi request reprint Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment
    Silvana Borges
    Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, 46202, USA
    Clin Pharmacol Ther 80:61-74. 2006
    ..We conducted a prospective trial in 158 patients with breast cancer who were taking tamoxifen to further understand the effect of CYP2D6 genotype and concomitant medications on endoxifen plasma concentrations...
  32. ncbi request reprint Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro
    Zeruesenay Desta
    Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 1001 West 10th Street, WD Myers Bldg, W7123, Indianapolis, IN 46202, USA
    Pharmacogenomics 8:547-58. 2007
    ..To determine the influence of cytochrome P450 2B6 (CYP2B6) genotype on the rate of oxidative efavirenz metabolism in human liver microsomes...
  33. ncbi request reprint Association of polymorphisms of angiogenesis genes with breast cancer
    Bryan P Schneider
    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
    Breast Cancer Res Treat 111:157-63. 2008
    ..We report our preliminary data evaluating the association of polymorphisms from seven genes known to influence angiogenesis with the likelihood of having breast cancer...
  34. doi request reprint Exploratory study evaluating the association of polymorphisms of angiogenesis genes with hot flashes
    Bryan P Schneider
    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
    Breast Cancer Res Treat 116:543-9. 2009
    ..We evaluated the association between germline polymorphisms in genes important to angiogenesis and subjective reporting of hot flashes...
  35. pmc Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100
    Bryan P Schneider
    Indiana University School of Medicine, Indianapolis, IN, USA
    J Clin Oncol 26:4672-8. 2008
    ..Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer...
  36. pmc A mixture model approach in gene-gene and gene-environmental interactions for binary phenotypes
    Lang Li
    Division of Biostatistics, Department of Medicine, Indiana University, Indianapolis, Indiana46202, USA
    J Biopharm Stat 18:1150-77. 2008
    ..The mixture model approach has the highest recovery probability to recover the true partition in the simulation studies. Its applications are exemplified in interim data analyses for two cancer studies...
  37. doi request reprint Pharmacokinetics of ibutilide in patients with heart failure due to left ventricular systolic dysfunction
    James E Tisdale
    Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Purdue University, 1001 W 10th Street, Indianapolis, IN, USA
    Pharmacotherapy 28:1461-70. 2008
    ....
  38. pmc Methadone: a substrate and mechanism-based inhibitor of CYP19 (aromatase)
    Wenjie Jessie Lu
    Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Drug Metab Dispos 38:1308-13. 2010
    ..Methadone is metabolized by CYP19 and may act as a potent inhibitor of CYP19 in vivo. These findings may contribute to variability in methadone clearance, to drug-drug interactions, and to side effects observed in individual patients...
  39. pmc Pharmacotherapy and pregnancy: highlights from the Second International Conference for Individualized Pharmacotherapy in Pregnancy
    David M Haas
    Indiana University School of Medicine, PREGMED, The Indiana University Center for Pharmacogenetics and Therapeutics Research in Maternal and Child Health, Indiana, USA
    Clin Transl Sci 2:439-43. 2009
    ....
  40. pmc Rapid identification of the hepatic cytochrome P450 2C19 activity using a novel and noninvasive [13C]pantoprazole breath test
    Zeruesenay Desta
    Indiana University School of Medicine, Indianapolis, IN 46202, USA
    J Pharmacol Exp Ther 329:297-305. 2009
    ..74; p = 0.038). These feasibility data suggest that the [(13)C]pantoprazole breath test is a reliable, rapid, and noninvasive probe of CYP2C19 and seems to be a useful tool to optimize drug therapy metabolized by CYP2C19...
  41. ncbi request reprint Association between the CYP3A5 genotype and blood pressure
    Herbert Ho
    Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 1001 W Tenth St, WD Myers Room W7123, Indianapolis, IN 46202, USA
    Hypertension 45:294-8. 2005
    ..We conclude that although untreated blood pressure may be higher in blacks with the CYP3A5*3/*3 genotype, the CYP3A5*1 allele may be associated with hypertension that is more refractory to treatment in this ethnic group...
  42. ncbi request reprint Induction of testosterone metabolism by esomeprazole in a CYP2C19*2 heterozygote
    Beth Rosenshein
    Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202 2879, USA
    Am J Med Sci 327:289-93. 2004
    ..The authors believe this to be the first case of female sexual dysfunction associated with esomeprazole described in the literature. They discuss a number of possible mechanisms for this effect...
  43. ncbi request reprint Effects of endothelial nitric oxide synthase gene polymorphisms on platelet function, nitric oxide release, and interactions with estradiol
    Jose E Tanus-Santos
    Division of Clinical Pharmacology, Georgetown University Medical School, Washington, DC, USA
    Pharmacogenetics 12:407-13. 2002
    ....
  44. ncbi request reprint In vitro inhibition of pimozide N-dealkylation by selective serotonin reuptake inhibitors and azithromycin
    Zeruesenay Desta
    Division of Clinical Pharmacology, Department of Medicine, Georgetown University Medical Center, Washington, DC, USA
    J Clin Psychopharmacol 22:162-8. 2002
    ..In addition, the possibility that these drugs could alter pimozide disposition through effects on transport proteins or via promoter repression cannot be ruled out...
  45. ncbi request reprint Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6
    Zeruesenay Desta
    Indiana University School of Medicine, Department of Medicine Division of Clinical Pharmacology, 1001 West 10th Street, WD Myers Bldg, W7123, Indianapolis, IN 46202, USA
    J Pharmacol Exp Ther 310:1062-75. 2004
    ..Variable activity of these P450s, brought about by genetic polymorphisms and drug interactions, may alter the balance of TAM effects in vivo...
  46. ncbi request reprint The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity
    Bryan A Ward
    Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    J Pharmacol Exp Ther 306:287-300. 2003
    ..Efavirenz may be a valuable phenotyping tool to study the role of CYP2B6 in human drug metabolism...
  47. ncbi request reprint Cytochrome P450 3A pharmacogenetics: the road that needs traveled
    D A Flockhart
    Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis 46202, USA
    Pharmacogenomics J 3:3-5. 2003
  48. ncbi request reprint Enhancing race-based prescribing precision with pharmacogenomics
    A Nguyen
    Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Clin Pharmacol Ther 81:323-5. 2007
    ....
  49. ncbi request reprint Analysis of angiogenesis genes from paraffin-embedded breast tumor and lymph nodes
    Bryan P Schneider
    Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
    Breast Cancer Res Treat 96:209-15. 2006
    ..These genes include vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS)...
  50. doi request reprint Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin
    David A Flockhart
    Indiana University School of Medicine, Indianapolis, Indiana, USA
    Genet Med 10:139-50. 2008
    ....
  51. ncbi request reprint Clinical significance of the cytochrome P450 2C19 genetic polymorphism
    Zeruesenay Desta
    Division of Clinical Pharmacology, Indiana University School of Medicine, Wishard Hospital, Indianapolis 46202, USA
    Clin Pharmacokinet 41:913-58. 2002
    ..Finally, many studies have attempted to identify relationships between CYP2C19 genotype and phenotype and susceptibility to xenobiotic-induced disease, but none of these are compelling...
  52. pmc Estrogen receptor genotypes influence hot flash prevalence and composite score before and after tamoxifen therapy
    Yan Jin
    Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
    J Clin Oncol 26:5849-54. 2008
    ..We determined whether genetic polymorphisms in estrogen receptors (ESRs) alpha and beta (ESR1 and ESR2, respectively) are associated with tamoxifen-induced hot flashes...
  53. pmc Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro
    Bryan A Ward
    Indiana University School of Medicine, Department of Medicine Division of Clinical Pharmacology, 1001 West 10th Street, OPD W 320, Indianapolis, Indiana, USA
    Br J Clin Pharmacol 58:277-87. 2004
    ..To confirm the identity of the major metabolites of domperidone and to characterize the cytochrome P450s (CYPs) involved in their formation...
  54. pmc Genome-wide discovery of genetic variants affecting tamoxifen sensitivity and their clinical and functional validation
    L Weng
    Department of Medicine
    Ann Oncol 24:1867-73. 2013
    ..We utilized a genome-wide cell-based model to comprehensively evaluate genetic variants for their contribution to cellular sensitivity to TAM...
  55. ncbi request reprint The gastroprokinetic and antiemetic drug metoclopramide is a substrate and inhibitor of cytochrome P450 2D6
    Zeruesenay Desta
    Division of Clinical Pharmacology, Department of Medicine, Georgetown University Medical Center, Washington, DC, USA
    Drug Metab Dispos 30:336-43. 2002
    ..Metoclopramide elimination is likely to be slowed in poor metabolizers of CYP2D6 or in patients taking inhibitors of this isoform, whereas metoclopramide itself could reduce the clearance of CYP2D6 substrate drugs...
  56. ncbi request reprint Selection of drugs to treat gastro-oesophageal reflux disease: the role of drug interactions
    D A Flockhart
    Division of Clinical Pharmacology, Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA
    Clin Pharmacokinet 39:295-309. 2000
    ..Cisapride is clearly able to prolong the electrocardiographic QT interval and cause lethal ventricular arrhythmias when its metabolism is slowed by interaction with inhibitors of CYP3A, such as erythromycin, ketoconazole or itraconazole...
  57. ncbi request reprint Sequence diversity and functional characterization of the 5'-regulatory region of human CYP2C19
    Million Arefayene
    Department of Medicine Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Pharmacogenetics 13:199-206. 2003
    ..These data make possible future studies to elucidate the molecular mechanisms by which CYP2C19 can be induced in clinical settings and the consequences of genetic variability in its promoter...
  58. ncbi request reprint Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen
    Young Chai Lim
    Division of Clinical Pharmacology, Indiana University School of Medicine, 1001 West 10th Street, WD Myers Bldg, W7123, Indianapolis, Indiana 46202, USA
    Cancer Chemother Pharmacol 55:471-8. 2005
    ..We, therefore, determined the effect of endoxifen and 4-OH-Tam on 17beta-estradiol (E2)-induced PR mRNA expression in an estrogen receptor-positive human breast cancer cell line...
  59. ncbi request reprint Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient
    C J Rosebraugh
    Department of Pharmacology and Medicine, Division of Clinical Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA
    J Clin Pharmacol 41:224-7. 2001
    ..Possible pharmacological mechanisms are discussed. In complicated patients that are taking multiple medications, physicians should be aware of this possible interaction to avoid delay in the diagnosis of serotonin syndrome...
  60. ncbi request reprint Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants
    J E Tanus-Santos
    Division of Clinical Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA
    Pharmacogenetics 11:719-25. 2001
    ....
  61. pmc High-level expression of EphA2 receptor tyrosine kinase in prostatic intraepithelial neoplasia
    Guangyuan Zeng
    Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Am J Pathol 163:2271-6. 2003
    ..Moreover, the presence of high levels of EphA2 in these cells suggests opportunities for prostate cancer prevention and treatment...
  62. doi request reprint Differential quantification of CYP2D6 gene copy number by four different quantitative real-time PCR assays
    Anuradha Ramamoorthy
    Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Pharmacogenet Genomics 20:451-4. 2010
    ..Selective amplification of non-CYP2D6*36 sequence by the Ex9 assay should be useful in determining the number of functional copies of CYP2D6 in Asian populations...
  63. ncbi request reprint Effect of cirrhosis and liver transplantation on the gender difference in QT interval
    Adegboyega Q Adigun
    Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Am J Cardiol 95:691-4. 2005
    ..The study showed that (1) physiologic gender difference in the QTc interval is abolished in cirrhosis, and it is not restored after liver transplantation, and (2) gender hormone concentrations had no effect on the QTc interval...
  64. ncbi request reprint Quantification of tamoxifen and three metabolites in plasma by high-performance liquid chromatography with fluorescence detection: application to a clinical trial
    Kyung Hoon Lee
    Division of Clinical Pharmacology, Indiana University School of Medicine, Wishard Memorial Hospital, 1001 West Tenth Street, Myers Building W7123, Indianapolis, IN 46202, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 791:245-53. 2003
    ..B 655 (1994) 261]. The coefficients of variation for the midpoint of the standard curve for each compound were less than 10%. This method was applied to a pharmacokinetic study of tamoxifen disposition in breast cancer patients...
  65. ncbi request reprint The unfinished business of U.S. drug safety regulation
    Barbara J Evans
    Program in Pharmacogenomics, Ethics, and Public Policy, Indiana University Center for Bioethics, Indianapolis, IN, USA
    Food Drug Law J 61:45-63. 2006
  66. ncbi request reprint Creating incentives for genomic research to improve targeting of therapies
    Barbara J Evans
    Pharmacogenomics, Ethics, and Public Policy Program, Indiana University Center for Bioethics, Indianapolis, USA
    Nat Med 10:1289-91. 2004
  67. ncbi request reprint Identification of genetic variants in the human indoleamine 2,3-dioxygenase (IDO1) gene, which have altered enzyme activity
    Million Arefayene
    Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Pharmacogenet Genomics 19:464-76. 2009
    ..We identified genetic variations in the IDO1 gene and evaluated their functional activities using in-vitro transfection studies...
  68. ncbi request reprint Pharmacokinetics of fluvoxamine in relation to CYP2C19 phenotype and genotype
    Michael W Jan
    Department of Pharmacy Practice and Pharmaceutical Sciences, Mercer University, Southern School of Pharmacy, Atlanta, GA 30341, USA
    Drug Metabol Drug Interact 19:1-11. 2002
    ..To evaluate the pharmacokinetics of fluvoxamine (FLV) in poor metabolizers (PMs) versus extensive metabolizers (EMs) of cytochrome P450 (CYP)2C19...
  69. ncbi request reprint Effects of CYP2C19 and CYP2C9 genetic polymorphisms on the disposition of and blood glucose lowering response to tolbutamide in humans
    Ji Hong Shon
    Department of Pharmacology, Inje University College of Medicine and Clinical Pharmacology Center, Pusan Paik Hospital, Pusan, South Korea
    Pharmacogenetics 12:111-9. 2002
    ..The in-vivo contribution of CYP2C19 to tolbutamide 4-methylhydroxylation appears to be minor in humans. This suggests that, at least in vivo, tolbutamide remains a selective probe for measuring CYP2C9 activity in humans...
  70. ncbi request reprint Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin
    Jae Gook Shin
    Department of Pharmacology, Inje University College of Medicine and Clinical Pharmacology Center, Busan Paik Hospital, Busan, Seoul, Korea
    Drug Metab Dispos 30:1102-7. 2002
    ..These results suggest that TCAs inhibit both CYP2D6 and CYP2C19 and that the interaction between TCAs and phenytoin involves inhibition of CYP2C19-catalyzed phenytoin p-hydroxylation...
  71. ncbi request reprint Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis
    Kazuki Takada
    National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA
    Arthritis Rheum 50:2202-10. 2004
    ..We conducted a retrospective cohort study to test whether genetic polymorphisms of these enzymes are associated with the toxicity of, and clinical response to, cyclophosphamide in patients with lupus nephritis...
  72. pmc Drug interactions and pharmacogenomics in the treatment of breast cancer and depression
    N Lynn Henry
    Breast Oncology Program, University of Michigan Comprehensive Cancer Center, 300 North Ingalls St, Bldg 3A04, Ann Arbor, MI 48109 5419, USA
    Am J Psychiatry 165:1251-5. 2008
  73. ncbi request reprint The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen
    Matthew P Goetz
    Department of Oncology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN, 55905, USA
    Breast Cancer Res Treat 101:113-21. 2007
    ....
  74. ncbi request reprint Interethnic differences in genetic polymorphisms of CYP2D6 in the U.S. population: clinical implications
    Stephen Bernard
    Division of Hematology and Medical Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7305, USA
    Oncologist 11:126-35. 2006
    ..The CYP2D6 polymorphism may become more important as robust clinical tests become widely available and as the use of multiple medications and the attendant risk for drug-drug interactions increases...
  75. ncbi request reprint Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism
    Pascal Le Corre
    Laboratoire de Pharmacie Galenique et Biopharmacie, Universite de Rennes I, Rennes, France
    Clin Pharmacol Ther 76:139-53. 2004
    ..alpha2-Adrenergic blockade responses suggest adrenergic dysfunction in hypertension. alpha2-Blockade is also used to treat autonomic dysfunction. However, pharmacokinetic determinants of yohimbine disposition are not understood...
  76. pmc Germline pharmacogenetics of tamoxifen response: have we learned enough?
    Zeruesenay Desta
    J Clin Oncol 25:5147-9. 2007
  77. ncbi request reprint Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen
    Michael D Johnson
    Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA
    Breast Cancer Res Treat 85:151-9. 2004
    ....
  78. pmc Cytochrome P450 2D6 and homeobox 13/interleukin-17B receptor: combining inherited and tumor gene markers for prediction of tamoxifen resistance
    Matthew P Goetz
    Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Clin Cancer Res 14:5864-8. 2008
    ..We sought to determine the combined effect of inherited (CYP2D6) and somatic (HOXB13/IL17BR) gene variation in tamoxifen-treated breast cancer...
  79. ncbi request reprint Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes
    Matthew P Goetz
    Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    J Clin Oncol 23:9312-8. 2005
    ..Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown...
  80. ncbi request reprint Endothelial nitric oxide synthase haplotypes are related to blood pressure elevation, but not to resistance to antihypertensive drug therapy
    Valeria C Sandrim
    Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil
    J Hypertens 24:2393-7. 2006
    ..Although endothelial nitric oxide synthase (eNOS) haplotypes have been associated with hypertension, it is unknown whether eNOS genotypes/haplotypes are associated with resistance to antihypertensive therapy...
  81. ncbi request reprint The effects of tamoxifen and its metabolites on platelet function and release of reactive oxygen intermediates
    Olga Vitseva
    Boston University School of Medicine, 715 Albany St, W507, Boston, MA 02118, USA
    J Pharmacol Exp Ther 312:1144-50. 2005
    ..This results in modest changes in platelet function and seems to be consistent with previous oncological studies demonstrating tamoxifen-dependent increase in reactive oxygen species generation...
  82. ncbi request reprint Breast cancer treatment and ovarian failure: risk factors and emerging genetic determinants
    Vered Stearns
    Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
    Nat Rev Cancer 6:886-93. 2006
    ..Because inherited genetic factors have an important role in determining who will experience CIOF, genetic testing has the potential to provide optimal counselling about risks and possible interventions...
  83. pmc Possible interethnic differences in quinidine-induced QT prolongation between healthy Caucasian and Korean subjects
    Jae Gook Shin
    Department of Pharmacology and Pharmacogenomics Research Centre, Inje University College of Medicine, Busan, Korea
    Br J Clin Pharmacol 63:206-15. 2007
    ....
  84. ncbi request reprint Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men
    Ingrid F Metzger
    Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil
    Pharmacogenet Genomics 15:565-70. 2005
    ..In this study we compared the distribution of haplotypes involving three relevant eNOS polymorphisms (T-786C in the promoter region; b/a in intron 4, and Glu298Asp in exon 7) in healthy subjects with low and high circulating NOx levels...
  85. ncbi request reprint Pharmacogenomics: challenges and opportunities
    Dan M Roden
    Vanderbilt University, Nashville, Tennessee, USA
    Ann Intern Med 145:749-57. 2006
    ..Overcoming these challenges holds the promise of improving new drug development and ultimately individualizing the selection of appropriate drugs and dosages for individual patients...
  86. pmc Creating and evaluating genetic tests predictive of drug response
    Scott T Weiss
    Channing Laboratory, Brigham and Women s Hospital, 181 Longwood Ave, Boston, Massachusetts 02115, USA
    Nat Rev Drug Discov 7:568-74. 2008
    ....
  87. ncbi request reprint Genotyping for polymorphic drug metabolizing enzymes from paraffin-embedded and immunohistochemically stained tumor samples
    James M Rae
    Division of Hematology Oncology, Department of Internal Medicine, University of Michigan Medical Center, 5323 Med Sci 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA
    Pharmacogenetics 13:501-7. 2003
    ..We set out to establish genotyping methods for relevant genes from archival tumor samples and determine if fixation, processing or somatic changes in the tumor might affect our ability to identify germ-line polymorphisms...
  88. ncbi request reprint Drug-metabolizing enzymes: evidence for clinical utility of pharmacogenomic tests
    Tommy Andersson
    Clinical Pharmacology, AstraZeneca, Molndal
    Clin Pharmacol Ther 78:559-81. 2005

Research Grants3

  1. MECHANISMS OF CARDIOTOXICITY OF ANTIPSYCHOTIC DRUGS
    David Flockhart; Fiscal Year: 2001
    ....