Nina Isoherranen

Summary

Affiliation: University of Washington
Country: USA

Publications

  1. ncbi request reprint The influence of CYP3A5 expression on the extent of hepatic CYP3A inhibition is substrate-dependent: an in vitro-in vivo evaluation
    Nina Isoherranen
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA
    Drug Metab Dispos 36:146-54. 2008
  2. pmc Substrate specificity and ligand interactions of CYP26A1, the human liver retinoic acid hydroxylase
    Jayne E Thatcher
    Department of Pharmaceutics, Box 357610, University of Washington, Seattle, WA 98195, USA
    Mol Pharmacol 80:228-39. 2011
  3. pmc Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases
    Ariel R Topletz
    Department of Pharmaceutics, University of Washington, Seattle, United States
    Biochem Pharmacol 83:149-63. 2012
  4. doi request reprint Quantitative prediction of CYP2B6 induction by estradiol during pregnancy: potential explanation for increased methadone clearance during pregnancy
    Leslie J Dickmann
    Department of Pharmacokineticsand Drug Metabolism, Amgen
    Drug Metab Dispos 41:270-4. 2013
  5. pmc Importance of multi-p450 inhibition in drug-drug interactions: evaluation of incidence, inhibition magnitude, and prediction from in vitro data
    Nina Isoherranen
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Box 357610, Seattle, WA 98195, USA
    Chem Res Toxicol 25:2285-300. 2012
  6. pmc Drug Metabolism and Transport During Pregnancy: How Does Drug Disposition Change during Pregnancy and What Are the Mechanisms that Cause Such Changes?
    Nina Isoherranen
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195 7610
    Drug Metab Dispos 41:256-62. 2013
  7. pmc Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database
    Nina Isoherranen
    Department of Pharmaceutics, University of Washington, P O Box 357610, Seattle, Washington 98195, USA
    Chem Res Toxicol 22:294-8. 2009
  8. pmc Expression and functional characterization of cytochrome P450 26A1, a retinoic acid hydroxylase
    Justin D Lutz
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA
    Biochem Pharmacol 77:258-68. 2009
  9. pmc Risk assessment of mechanism-based inactivation in drug-drug interactions
    Yasushi Fujioka
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA
    Drug Metab Dispos 40:1653-7. 2012
  10. pmc Stereospecific metabolism of itraconazole by CYP3A4: dioxolane ring scission of azole antifungals
    Chi Chi Peng
    Department of Pharmaceutics, University of Washington, P O Box 357610, Seattle, Washington 98103, USA
    Drug Metab Dispos 40:426-35. 2012

Collaborators

Detail Information

Publications33

  1. ncbi request reprint The influence of CYP3A5 expression on the extent of hepatic CYP3A inhibition is substrate-dependent: an in vitro-in vivo evaluation
    Nina Isoherranen
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA
    Drug Metab Dispos 36:146-54. 2008
    ..In conclusion, the effect of CYP3A5 on hepatic CYP3A-mediated inhibitory drug-drug interactions is substrate-dependent, and HLM, rather than rCYP3A, are the preferred in vitro system for predicting these interactions in vivo...
  2. pmc Substrate specificity and ligand interactions of CYP26A1, the human liver retinoic acid hydroxylase
    Jayne E Thatcher
    Department of Pharmaceutics, Box 357610, University of Washington, Seattle, WA 98195, USA
    Mol Pharmacol 80:228-39. 2011
    ..7, 4.2, and 8.6 μM, respectively. These data demonstrate that CYP26A1 has high ligand selectivity but accepts structurally related nuclear receptor agonists as inhibitors...
  3. pmc Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases
    Ariel R Topletz
    Department of Pharmaceutics, University of Washington, Seattle, United States
    Biochem Pharmacol 83:149-63. 2012
    ..CYP26A1 has higher catalytic activity than CYP26B1 and seems to be responsible for metabolism of atRA in tissues that function as a barrier for atRA exposure...
  4. doi request reprint Quantitative prediction of CYP2B6 induction by estradiol during pregnancy: potential explanation for increased methadone clearance during pregnancy
    Leslie J Dickmann
    Department of Pharmacokineticsand Drug Metabolism, Amgen
    Drug Metab Dispos 41:270-4. 2013
    ..This could in part explain the observed increase in methadone clearance during pregnancy...
  5. pmc Importance of multi-p450 inhibition in drug-drug interactions: evaluation of incidence, inhibition magnitude, and prediction from in vitro data
    Nina Isoherranen
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Box 357610, Seattle, WA 98195, USA
    Chem Res Toxicol 25:2285-300. 2012
    ..The results of this study suggest that inhibition of multiple clearance pathways in vivo is clinically relevant, and the risk of DDIs with object drugs may be best evaluated in studies using multi-P450 inhibitors...
  6. pmc Drug Metabolism and Transport During Pregnancy: How Does Drug Disposition Change during Pregnancy and What Are the Mechanisms that Cause Such Changes?
    Nina Isoherranen
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195 7610
    Drug Metab Dispos 41:256-62. 2013
    ..The studies provide the impetus for a mechanism- and evidence-based approach to optimally managing drug therapies during pregnancy and improving treatment outcomes...
  7. pmc Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database
    Nina Isoherranen
    Department of Pharmaceutics, University of Washington, P O Box 357610, Seattle, Washington 98195, USA
    Chem Res Toxicol 22:294-8. 2009
    ....
  8. pmc Expression and functional characterization of cytochrome P450 26A1, a retinoic acid hydroxylase
    Justin D Lutz
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA
    Biochem Pharmacol 77:258-68. 2009
    ..These results provide a biochemical framework for CYP26A1 function and offer insight into the role of CYP26A1 as a drug target as well as in fetal development and cell cycle regulation...
  9. pmc Risk assessment of mechanism-based inactivation in drug-drug interactions
    Yasushi Fujioka
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA
    Drug Metab Dispos 40:1653-7. 2012
    ..However, the use of total C(max) led to great overprediction of DDI risk. The risk assessment using λ/k(deg) coupled with unbound C(max) can be useful for the DDI risk evaluation of MBIs in drug discovery and development...
  10. pmc Stereospecific metabolism of itraconazole by CYP3A4: dioxolane ring scission of azole antifungals
    Chi Chi Peng
    Department of Pharmaceutics, University of Washington, P O Box 357610, Seattle, Washington 98103, USA
    Drug Metab Dispos 40:426-35. 2012
    ..These data suggest that the dioxolane ring scission is a metabolic pathway for drugs that contain this moiety...
  11. ncbi request reprint Stereochemical aspects of itraconazole metabolism in vitro and in vivo
    Kent L Kunze
    Department of Pharmaceutics, H272 Health Sciences Building, Box 357610, University of Washington, Seattle, WA 98195, USA
    Drug Metab Dispos 34:583-90. 2006
    ..However, stereoselective elimination was diminished after multiple dosing, presumably as a result of CYP3A4 autoinhibition. In conclusion, the metabolism of ITZ is highly stereoselective in vitro and in vivo...
  12. pmc The relative importance of CYP26A1 in hepatic clearance of all-trans retinoic acid
    Jayne E Thatcher
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, United States
    Biochem Pharmacol 80:903-12. 2010
    ..07L/min using combined Supersome data) was similar to the published in vivo clearance of RA. These findings suggest that CYP26A1 is the P450 isoform that should be targeted when designing RA metabolism blocking agents...
  13. pmc Hepatic Cyp2d and Cyp26a1 mRNAs and activities are increased during mouse pregnancy
    Ariel R Topletz
    School of Pharmacy, Department of Pharmaceutics, University of Washington, Seattle, WA 98195 7610, USA
    Drug Metab Dispos 41:312-9. 2013
    ..Our findings also suggest that retinoic acid signaling in the liver is increased during pregnancy, which may have broader implications to energy homeostasis in the liver during pregnancy...
  14. doi request reprint In vitro-to-in vivo predictions of drug-drug interactions involving multiple reversible inhibitors
    Justin D Lutz
    University of Washington School of Pharmacy, Department of Pharmaceutics, Seattle, WA, USA
    Expert Opin Drug Metab Toxicol 8:449-66. 2012
    ..This review provides the framework for predicting inhibitory DDIs of multiple inhibitors with any combination of reversible inhibition mechanism...
  15. pmc Surface plasmon resonance analysis of antifungal azoles binding to CYP3A4 with kinetic resolution of multiple binding orientations
    Josh T Pearson
    Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195 7610, USA
    Biochemistry 45:6341-53. 2006
    ..Most importantly, they provide the first example of a SPR-based method for the kinetic characterization of binding of a drug to any human CYP, including mechanistic insight not available from other methods...
  16. pmc Stereoselective formation and metabolism of 4-hydroxy-retinoic Acid enantiomers by cytochrome p450 enzymes
    Jakob A Shimshoni
    Department of Pharmaceutics, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 287:42223-32. 2012
    ..The stereoselectivity observed in CYP26A1 function will aid in better understanding of the active site features of the enzyme and the disposition of biologically active retinoids...
  17. pmc Contributions of human cytochrome P450 enzymes to glyburide metabolism
    Lin Zhou
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA
    Biopharm Drug Dispos 31:228-42. 2010
    ..These results confirm that human CYP3A4 is the major enzyme involved in the in vitro metabolism of GLB...
  18. ncbi request reprint Evidence of significant contribution from CYP3A5 to hepatic drug metabolism
    Weili Huang
    Department of Pharmaceutics, Box 357610, University of Washington, Seattle, WA 98195 7610, USA
    Drug Metab Dispos 32:1434-45. 2004
    ..We suggest that, under conditions when CYP3A5 content represents a significant fraction of the total hepatic CYP3A pool, the contribution of CYP3A5 to the clearance of some drugs may be an important source of interindividual variability...
  19. pmc Identification of human UDP-glucuronosyltransferases catalyzing hepatic 1alpha,25-dihydroxyvitamin D3 conjugation
    Takanori Hashizume
    Department of Pharmaceutics, University of Washington, Seattle, WA, United States
    Biochem Pharmacol 75:1240-50. 2008
    ..If enterohepatic recycling of 1,25(OH)2D3 represents a significant component of intestinal and systemic 1,25(OH)2D3 disposition, formation of monoglucuronides by hepatic UGT1A4 constitutes an important initial step...
  20. pmc A comparison of the roles of peroxisome proliferator-activated receptor and retinoic acid receptor on CYP26 regulation
    Suzanne Tay
    Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA
    Mol Pharmacol 77:218-27. 2010
    ..The fact that drugs can alter the expression of CYP26 enzymes may have toxicological and therapeutic importance...
  21. pmc Changes in maternal liver Cyp2c and Cyp2d expression and activity during rat pregnancy
    Leslie J Dickmann
    Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA
    Biochem Pharmacol 75:1677-87. 2008
    ..These data show that pregnancy significantly alters the expression and activity of drug metabolizing enzymes in an enzyme and gestational stage specific manner. These changes are likely to have toxicological and therapeutic implications...
  22. ncbi request reprint Effect of CYP3A5 polymorphism on tacrolimus metabolic clearance in vitro
    Yang Dai
    Department of Pharmaceutics, University of Washington, Seattle, 98195 7610, USA
    Drug Metab Dispos 34:836-47. 2006
    ..These data suggest that CYP3A5 contributes significantly to the metabolic clearance of tacrolimus in the liver and kidney...
  23. pmc Effect of CYP3A5 expression on the inhibition of CYP3A-catalyzed drug metabolism: impact on modeling CYP3A-mediated drug-drug interactions
    Yoshiyuki Shirasaka
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA
    Drug Metab Dispos 41:1566-74. 2013
    ....
  24. pmc The role of CYP26 enzymes in retinoic acid clearance
    Jayne E Thatcher
    University of Washington, Department of Pharmaceutics, School of Pharmacy, Seattle, WA 98195, USA
    Expert Opin Drug Metab Toxicol 5:875-86. 2009
    ..To further the understanding of how CYP26 enzymes contribute to the regulation of RA homeostasis, structural information of the CYP26s, commercially available recombinant enzymes and good specific and sensitive antibodies are needed...
  25. pmc The role of metabolites in predicting drug-drug interactions: focus on irreversible cytochrome P450 inhibition
    Brooke M VandenBrink
    University of Washington, Department of Medicinal Chemistry, Box 357610, Seattle, WA 98195, USA
    Curr Opin Drug Discov Devel 13:66-77. 2010
    ..Data discussed in this review suggest that circulating metabolites are more important in CYP inhibition in vivo than has been acknowledged...
  26. ncbi request reprint Role of itraconazole metabolites in CYP3A4 inhibition
    Nina Isoherranen
    University of Washington, Department of Pharmaceutics, H272 Health Sciences Building, Box 357610, Seattle, WA 98195 7610, USA
    Drug Metab Dispos 32:1121-31. 2004
    ..These findings demonstrate that ITZ metabolites are as potent as or more potent CYP3A4 inhibitors than ITZ itself, and thus may contribute to the inhibition of CYP3A4 observed in vivo after ITZ dosing...
  27. pmc Rationalization and prediction of in vivo metabolite exposures: the role of metabolite kinetics, clearance predictions and in vitro parameters
    Justin D Lutz
    Department of Pharmaceutics, University of Washington, School of Pharmacy, H272 Health Science Building, Box 357610, Seattle, WA 98195 7610, USA
    Expert Opin Drug Metab Toxicol 6:1095-109. 2010
    ..However, limited tools are available to quantitatively predict their human exposures...
  28. pmc A sensitive and specific method for measurement of multiple retinoids in human serum with UHPLC-MS/MS
    Samuel L M Arnold
    Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA
    J Lipid Res 53:587-98. 2012
    ..11-cisRA and 4OH-RA were not detected in human serum. The high sensitivity of the MS/MS method combined with the UHPLC separation power allowed detection of endogenous 9-cisRA and 4oxo-atRA for the first time in human serum...
  29. pmc Pregnancy decreases rat CYP1A2 activity and expression
    Alysa A Walker
    Department of Pharmaceutics, University of Washington, Seattle, Washington 98195 7610, USA
    Drug Metab Dispos 39:4-7. 2011
    ....
  30. pmc Inhibition of CYP2C19 and CYP3A4 by omeprazole metabolites and their contribution to drug-drug interactions
    Yoshiyuki Shirasaka
    Department of Pharmaceutics, School of Pharmacy, University of Washington, University of Washington, Seattle, WA, USA
    Drug Metab Dispos 41:1414-24. 2013
    ..The results of this study show that, although metabolites contribute to in vivo DDIs, their relative abundance in circulation or logP values do not predict their contribution to in vivo DDI risk...
  31. pmc A Physiologically Based Pharmacokinetic Model to Predict Disposition of CYP2D6 and CYP1A2 Metabolized Drugs in Pregnant Women
    Alice Ban Ke
    Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195
    Drug Metab Dispos 41:801-13. 2013
    ..Based on these data, it is prudent to conclude that the magnitude of hepatic CYP2D6 induction during T3 ranges from 100 to 200%. Our PBPK model can predict the disposition of CYP1A2, 2D6, and 3A drugs during pregnancy...
  32. pmc Prediction of relative in vivo metabolite exposure from in vitro data using two model drugs: dextromethorphan and omeprazole
    Justin D Lutz
    School of Pharmacy, Department of Pharmaceutics, University of Washington, Seattle, WA 98195 7610, USA
    Drug Metab Dispos 40:159-68. 2012
    ..This study shows that relative in vivo metabolite exposure can be predicted from in vitro data and characterization of secondary metabolism of probe metabolites is critical for interpretation of phenotypic data...
  33. pmc Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis
    John K Amory
    Department of Medicine, University of Washington School of Medicine and School of Pharmaceutics, Seattle, WA 98195, USA
    J Androl 32:111-9. 2011
    ..These findings suggest that ALDH1a2 is a promising target for the development of a reversible, nonhormonal male contraceptive...

Research Grants4

  1. Effects of Xenobiotics on CYP26 Activity and Retinoic Acid Homeostasis
    Nina Isoherranen; Fiscal Year: 2010
    ..This proposal aims at characterizing interactions between xenobiotics and retinoic acid metabolizing CYP26 enzymes that alter retinoic acid metabolism and clearance and can lead to adverse effects. ..
  2. Effects of Xenobiotics on CYP26 Activity and Retinoic Acid Homeostasis
    Nina Isoherranen; Fiscal Year: 2009
    ..This proposal aims at characterizing interactions between xenobiotics and retinoic acid metabolizing CYP26 enzymes that alter retinoic acid metabolism and clearance and can lead to adverse effects. ..
  3. Effects of Xenobiotics on CYP26 Activity and Retinoic Acid Homeostasis
    Nina Isoherranen; Fiscal Year: 2009
    ..This proposal aims at characterizing interactions between xenobiotics and retinoic acid metabolizing CYP26 enzymes that alter retinoic acid metabolism and clearance and can lead to adverse effects. ..