David J Greenblatt

Summary

Affiliation: Tufts University
Country: USA

Publications

  1. ncbi request reprint Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts New England Medical Center, Boston, Mass, USA
    Clin Pharmacol Ther 79:125-33. 2006
  2. ncbi request reprint Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice
    David J Greenblatt
    Department of Pharmaacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Clin Pharmacol Ther 74:121-9. 2003
  3. ncbi request reprint Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice
    Dora Farkas
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Clin Pharmacol 47:286-94. 2007
  4. pmc Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men
    Joel O Olubodun
    Department of Pharmacology and Experimental Therapeutics and the Jean Mayer USDA Human Nutrition Research Center on Ageing, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Br J Clin Pharmacol 56:297-304. 2003
  5. ncbi request reprint Age and gender effects on the pharmacokinetics and pharmacodynamics of triazolam, a cytochrome P450 3A substrate
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Clin Pharmacol Ther 76:467-79. 2004
  6. ncbi request reprint Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: comparison with ritonavir
    Kerry E Culm-Merdek
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, and Tufts New England Medical Center, Boston, Mass 02111, USA
    Clin Pharmacol Ther 79:243-54. 2006
  7. ncbi request reprint Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir
    James L Weemhoff
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharm Pharmacol 55:381-6. 2003
  8. pmc Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
    Michael J Hanley
    Sackler Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences, Boston, MA 02111, USA
    Br J Clin Pharmacol 75:1041-52. 2013
  9. ncbi request reprint Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Clin Pharmacol 46:214-21. 2006
  10. ncbi request reprint UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: I. Identification of polymorphisms in the 5'-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation
    Soundararajan Krishnaswamy
    Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University, Boston, MA 02111, USA
    J Pharmacol Exp Ther 313:1331-9. 2005

Detail Information

Publications86

  1. ncbi request reprint Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts New England Medical Center, Boston, Mass, USA
    Clin Pharmacol Ther 79:125-33. 2006
    ..To address this question, the effect of cranberry juice and other beverages on CYP2C9 activity was evaluated in vitro and in vivo...
  2. ncbi request reprint Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice
    David J Greenblatt
    Department of Pharmaacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Clin Pharmacol Ther 74:121-9. 2003
    ..The time course of recovery from CYP3A inhibition after a single exposure to grapefruit juice is not clearly established...
  3. ncbi request reprint Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice
    Dora Farkas
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Clin Pharmacol 47:286-94. 2007
    ..3 and 1.5, respectively, and reduced oral clearance to 72% of control values. Thus, PJ does not alter clearance of intravenous or oral midazolam, whereas GFJ impairs clearance and elevates plasma levels of oral midazolam...
  4. pmc Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men
    Joel O Olubodun
    Department of Pharmacology and Experimental Therapeutics and the Jean Mayer USDA Human Nutrition Research Center on Ageing, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Br J Clin Pharmacol 56:297-304. 2003
    ..The influence of ageing on the pharmacokinetics of zolpidem, an extensively prescribed hypnotic medication, was evaluated in healthy human volunteers...
  5. ncbi request reprint Age and gender effects on the pharmacokinetics and pharmacodynamics of triazolam, a cytochrome P450 3A substrate
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Clin Pharmacol Ther 76:467-79. 2004
    ..Although the findings are consistent with reduced clearance of triazolam in elderly men, individual variability was large and was not explained by identifiable demographic or environmental factors...
  6. ncbi request reprint Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: comparison with ritonavir
    Kerry E Culm-Merdek
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, and Tufts New England Medical Center, Boston, Mass 02111, USA
    Clin Pharmacol Ther 79:243-54. 2006
    ..However, the effect of extended exposure to grapefruit juice on CYP3A activity is not established...
  7. ncbi request reprint Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir
    James L Weemhoff
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharm Pharmacol 55:381-6. 2003
    ..Although lopinavir is less potent than ritonavir as an inhibitor of CYP3A, lopinavir is nonetheless likely to contribute to net CYP3A inhibition in-vivo during treatment with the lopinavir-ritonavir combination...
  8. pmc Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
    Michael J Hanley
    Sackler Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences, Boston, MA 02111, USA
    Br J Clin Pharmacol 75:1041-52. 2013
    ..The present study evaluated the possibility of drug interactions involving blueberry juice (BBJ) and substrate drugs whose clearance is dependent on cytochromes P4503A (CYP3A) and P4502C9 (CYP2C9)...
  9. ncbi request reprint Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Clin Pharmacol 46:214-21. 2006
    ..These amounts were apparently too low to inhibit CYP2C9 function in vivo. The results confirm previous controlled clinical studies showing no effect of ginkgo on the kinetics or dynamics of warfarin...
  10. ncbi request reprint UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: I. Identification of polymorphisms in the 5'-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation
    Soundararajan Krishnaswamy
    Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University, Boston, MA 02111, USA
    J Pharmacol Exp Ther 313:1331-9. 2005
    ..In conclusion, although the identified UGT1A6 polymorphisms did not explain the observed glucuronidation variability, there does seem to be a significant role for environmental factors associated with alcohol consumption...
  11. ncbi request reprint Effect of age on in vitro triazolam biotransformation in male human liver microsomes
    Kiran C Patki
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharmacol Exp Ther 308:874-9. 2004
    ..Reduced V(max) and Cl(int) for TRZ hydroxylation and CYP3A protein in livers from elderly men suggest reduced CYP3A gene expression in this group...
  12. ncbi request reprint The effect of age on sildenafil biotransformation in rat and mouse liver microsomes
    Jill S Warrington
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Drug Metab Dispos 31:1306-9. 2003
    ..Although the role of specific CYP enzymes and the clearance values for this reaction may differ among species, age-related changes in these rodent models are consistent with the reduced clearance of SIL observed in human studies...
  13. pmc Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers
    Laurie P Volak
    Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA
    Br J Clin Pharmacol 75:450-62. 2013
    ..The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers...
  14. ncbi request reprint Factors influencing midazolam hydroxylation activity in human liver microsomes
    Ping He
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Drug Metab Dispos 34:1198-207. 2006
    ..In conclusion, the investigated genetic factors did not contribute substantially to the large interindividual variability in midazolam hydroxylation, although alcohol consumption has a discernable but modest influence...
  15. ncbi request reprint The effect of chronic lorazepam administration in aging mice
    Jeanne M Fahey
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and the Division of Clinical Pharmacology, Tufts New England Medical Center, Boston, MA 02111, USA
    Brain Res 1118:13-24. 2006
    ....
  16. ncbi request reprint Age-related differences in CYP3A expression and activity in the rat liver, intestine, and kidney
    Jill S Warrington
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharmacol Exp Ther 309:720-9. 2004
    ..In addition, changes in testosterone levels and NADPH reductase expression may contribute to age-related differences in hepatic CYP3A activity...
  17. ncbi request reprint Ethanol inhibits in-vitro metabolism of nifedipine, triazolam and testosterone in human liver microsomes
    Kiran C Patki
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts New England Medical Center, Boston, MA 02111, USA
    J Pharm Pharmacol 56:963-6. 2004
    ..The IC50 values obtained were lower than clinically relevant blood alcohol concentrations. In conclusion, ethanol is an inhibitor of human CYP3A metabolism and may contribute to clinically important interactions...
  18. ncbi request reprint Kinetics and dynamics of intravenous adinazolam, N-desmethyl adinazolam, and alprazolam in healthy volunteers
    Karthik Venkatakrishnan
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Clin Pharmacol 45:529-37. 2005
    ..Collectively, these results indicate that the benzodiazepine-like effects occurring after adinazolam administration are mediated by mainly NDMAD...
  19. ncbi request reprint Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes
    Leah M Hesse
    Clinical Pharmacology Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Pharmacogenetics 14:225-38. 2004
    ..In conclusion, the results of this study indicate that interindividual variability in bupropion hydroxylation is a consequence of interactions between environmental and genetic influences on CYP2B6 gene function...
  20. doi request reprint Mechanism of cytochrome P450-3A inhibition by ketoconazole
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, 136 Harrison Ave, Boston, MA 02111, USA
    J Pharm Pharmacol 63:214-21. 2011
    ..Ketoconazole is extensively used as an index inhibitor of cytochrome P450-3A (CYP3A) activity in vitro and in vivo, but the mechanism of ketoconazole inhibition of CYP3A still is not clearly established...
  21. ncbi request reprint Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts New England Medical Center, Boston MA, 02111, USA
    J Clin Pharmacol 43:414-22. 2003
    ..Thus short-term low-dose administration of ritonavir impairs oral clearance of trazodone and increases the occurrence of adverse reactions. The findings are consistent with impairment of CYP3A-mediated trazodone metabolism by ritonavir...
  22. pmc Inhibition of oral midazolam clearance by boosting doses of ritonavir, and by 4,4-dimethyl-benziso-(2H)-selenazine (ALT-2074), an experimental catalytic mimic of glutathione oxidase
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Br J Clin Pharmacol 68:920-7. 2009
    ..The viral protease inhibitor ritonavir is known to inhibit clearance of intravenous midazolam. * ALT-2074, a catalytic mimic of glutathione oxidase, inhibits human cytochrome P450 3A (CYP3A) isoforms in vitro...
  23. ncbi request reprint UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S)
    Soundararajan Krishnaswamy
    Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University, Boston, MA 02111, USA
    J Pharmacol Exp Ther 313:1340-6. 2005
    ....
  24. ncbi request reprint In vitro, pharmacokinetic, and pharmacodynamic interactions of ketoconazole and midazolam in the rat
    Tsutomu Kotegawa
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts New England Medical Center, 136 Harrison Avenue, Boston, MA 02111, USA
    J Pharmacol Exp Ther 302:1228-37. 2002
    ..Although the in vitro and in vivo characteristics of midazolam in rats incompletely parallel those in humans, the experimental model can be used to assess aspects of drug interactions having potential clinical importance...
  25. ncbi request reprint Genotype-phenotype associations of cytochrome P450 3A4 and 3A5 polymorphism with midazolam clearance in vivo
    Ping He
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA
    Clin Pharmacol Ther 77:373-87. 2005
    ..012). In conclusion, these results indicate that the genetic variants identified so far in the CYP3A4 and CYP3A5 genes have only a limited impact on CYP3A-mediated drug metabolism in vivo...
  26. pmc Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics
    Kerry E Culm-Merdek
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts New England Medical Center, 136 Harrison Avenue, Boston, MA 02111, USA
    Br J Clin Pharmacol 60:486-93. 2005
    ..Coadministration of fluvoxamine impairs the clearance of caffeine and prolongs its elimination half-life, which is attributable to inhibition of CYP1A2 by fluvoxamine. The clinical importance of this interaction is not established...
  27. doi request reprint Mechanism-based inhibition of human cytochrome P450-3A activity by grapefruit hybrids having low furanocoumarin content
    David J Greenblatt
    Sackler Program in Pharmacology and Experimental Therapeutics, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA
    Xenobiotica 42:1163-9. 2012
    ..Further study is needed to determine how low the FC content needs to be (or how high the IC(50) needs to be) to assure minimal risk of clinical interactions involving GFJ and CYP3A substrate drugs...
  28. ncbi request reprint UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver
    Michael H Court
    Comparative and Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts, USA
    J Pharmacol Exp Ther 310:656-65. 2004
    ..05). In conclusion, gender and D85Y genotype are identified as major determinants of S-oxazepam glucuronidation by human liver and may explain in part polymorphic oxazepam glucuronidation by human subjects...
  29. ncbi request reprint Ritonavir greatly impairs CYP3A activity in HIV infection with chronic viral hepatitis
    Tamsin A Knox
    Nutrition Infection Division, Department of Public Health and Family Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
    J Acquir Immune Defic Syndr 49:358-68. 2008
    ..Ritonavir is a powerful inhibitor of cytochrome P450 3A (CYP3A) that metabolizes many antiretrovirals. We examined the effect of ritonavir and of chronic viral hepatitis (CVH) status on CYP3A activity...
  30. pmc Role of NADPH-cytochrome P450 reductase and cytochrome-b5/NADH-b5 reductase in variability of CYP3A activity in human liver microsomes
    Lu Gan
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Drug Metab Dispos 37:90-6. 2009
    ..Consequently, while aging is associated with decreased CPR and b(5) expression in human livers, this effect does not contribute to CYP3A variability...
  31. ncbi request reprint Rapid assessment of P-glycoprotein inhibition and induction in vitro
    Michael D Perloff
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Pharm Res 20:1177-83. 2003
    ..17 clinically used compounds were screened for their inhibitory effect on P-glycoprotein (P-gp), which was compared with the drugs' inhibitory activity against CYP3A4. The same assay was used to study induction of P-gp activity...
  32. ncbi request reprint Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats
    Jill S Warrington
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharm Pharmacol 56:819-25. 2004
    ..Also, the relative specificity of the index substrates phenacetin (for CYP1A2) and chlorzoxazone (for CYP2E1) in man appears not to be applicable in rats...
  33. doi request reprint Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications
    David J Greenblatt
    Tufts University School of Medicine, Tufts Medical Center, Department of Molecular Physiology and Pharmacology, Sackler Program in Pharmacology and Experimental Therapeutics, 136 Harrison Avenue, Boston, MA 02111, USA
    Expert Opin Drug Metab Toxicol 8:1609-18. 2012
    ..Eszopiclone is the active S-enantiomer of R,S-zopiclone, and is a cyclopyrrolone hypnotic acting via the GABA-benzodiazepine receptor system. Nearly 6 million prescriptions for eszopiclone are written yearly in the United States...
  34. ncbi request reprint Interaction of triazolam and ketoconazole in P-glycoprotein-deficient mice
    Lisa L von Moltke
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Drug Metab Dispos 32:800-4. 2004
    ..KET impairs clearance of TRZ but does not increase tissue uptake. However, KET itself may be a substrate for efflux transport at the blood-brain barrier...
  35. ncbi request reprint In vitro interactions of water-soluble garlic components with human cytochromes p450
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts New England Medical Center, Boston, MA, USA
    J Nutr 136:806S-809S. 2006
    ..However available clinical evidence does not indicate CYP3A inhibition in vivo. The findings suggest that drug interactions involving inhibition of CYP3A enzymes by aged garlic extract are very unlikely...
  36. ncbi request reprint Dynamics and kinetics of a modified-release formulation of zolpidem: comparison with immediate-release standard zolpidem and placebo
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Clin Pharmacol 46:1469-80. 2006
    ..001). Thus, MR zolpidem produces sustained plasma levels compared to IR, with resulting enhancement of pharmacodynamic effects in the 3- to 6-hour post-dosage interval...
  37. ncbi request reprint Effect of zolpidem on human cytochrome P450 activity, and on transport mediated by P-glycoprotein
    Lisa L von Moltke
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Biopharm Drug Dispos 23:361-7. 2002
    ..The findings indicate that zolpidem is very unlikely to cause clinical drug interactions attributable to impairment of CYP activity or P-gp mediated transport...
  38. ncbi request reprint The influence of age and sex on the clearance of cytochrome P450 3A substrates
    Monette M Cotreau
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Clin Pharmacokinet 44:33-60. 2005
    ..In such cases, women primarily have higher clearance than men...
  39. ncbi request reprint Atazanavir: effects on P-glycoprotein transport and CYP3A metabolism in vitro
    Elke S Perloff
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Drug Metab Dispos 33:764-70. 2005
    ..D. 0.13) and 5.7 microM (S.D. 4.1), respectively. Thus, atazanavir is an inhibitor and inducer of P-gp as well as a potent inhibitor of CYP3A in vitro, suggesting a potential for atazanavir to cause drug-drug interactions in vivo...
  40. ncbi request reprint Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity
    Ping He
    Division of Clinical Pharmacology, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Clin Pharmacol 46:1356-69. 2006
    ..In conclusion, several hPXR polymorphisms have been identified that may have predictive value for oral midazolam clearance, particularly in African Americans...
  41. doi request reprint Gender has a small but statistically significant effect on clearance of CYP3A substrate drugs
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA
    J Clin Pharmacol 48:1350-5. 2008
    ..Thus gender has a small and statistically significant, although most likely clinically unimportant, influence on CYP3A phenotype for substrates not transported by P-gp...
  42. pmc Evidence for oxazepam as an in vivo probe of UGT2B15: oxazepam clearance is reduced by UGT2B15 D85Y polymorphism but unaffected by UGT2B17 deletion
    Xi He
    Laboratory of Comparative and Molecular Pharmacogenomics and Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Br J Clin Pharmacol 68:721-30. 2009
    ..We also determined the possible influence of a common deletion polymorphism in the gene encoding UGT2B17, which shows substantial substrate specificity overlap with UGT2B15...
  43. pmc Pharmocokinetics and pharmacodynamics of single-dose triazolam: electroencephalography compared with the Digit-Symbol Substitution Test
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts New England Medical Center, Boston, MA 02111, USA
    Br J Clin Pharmacol 60:244-8. 2005
    ....
  44. ncbi request reprint Ritonavir has minimal impact on the pharmacokinetic disposition of a single dose of bupropion administered to human volunteers
    Leah M Hesse
    Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Clin Pharmacol 46:567-76. 2006
    ..These findings indicate that short-term ritonavir dosing has only minimal impact on the pharmacokinetic disposition of a single dose of bupropion in healthy volunteers...
  45. ncbi request reprint Apparent active transport of MDMA is not mediated by P-glycoprotein: a comparison with MDCK and Caco-2 monolayers
    Kirk M Bertelsen
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Biopharm Drug Dispos 27:219-27. 2006
    ....
  46. ncbi request reprint Age and gender effects on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic agent acting via melatonin receptors MT1 and MT2
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts New England Medical Center, 136 Harrison Avenue, Boston, MA 02111, USA
    J Clin Pharmacol 47:485-96. 2007
    ..The usually recommended clinical dose of ramelteon (8 mg) does not require modification based on age or gender...
  47. ncbi request reprint Validation of serotonin (5-hydroxtryptamine) as an in vitro substrate probe for human UDP-glucuronosyltransferase (UGT) 1A6
    Soundararajan Krishnaswamy
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Drug Metab Dispos 31:133-9. 2003
    ..769; P < 0.001) (n = 52). In conclusion, these results indicate that serotonin is a highly selective in vitro probe substrate for human UGT1A6...
  48. ncbi request reprint In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5
    Kiran C Patki
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111
    Drug Metab Dispos 31:938-44. 2003
    ..Because the inhibitory potency of ketoconazole in rCYP3A5 is substantially less than in rCYP3A4 and HLMs, CYP3A5 is probably less important than CYP3A4 in drug-drug interactions involving ketoconazole and CYP3A substrates...
  49. ncbi request reprint Effect of bupropion on CYP2B6 and CYP3A4 catalytic activity, immunoreactive protein and mRNA levels in primary human hepatocytes: comparison with rifampicin
    Leah M Hesse
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharm Pharmacol 55:1229-39. 2003
    ..1 fold, while 10 microM bupropion minimally altered CYP2E1 protein (1.2 fold). Overall, results of this study suggest that multiple doses of bupropion are not likely to induce CYP2B6, 3A4 or 2E1 in-vivo in man...
  50. ncbi request reprint Kinetics and EEG effects of midazolam during and after 1-minute, 1-hour, and 3-hour intravenous infusions
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Clin Pharmacol 44:605-11. 2004
    ..Despite the delay in effect onset during the 1-minute midazolam infusion, midazolam infusions in duration of up to 3 hours produce CNS sedation without evidence of tolerance...
  51. doi request reprint Comparison of pharmacokinetic profiles of zolpidem buffered sublingual tablet and zolpidem oral immediate-release tablet: results from a single-center, single-dose, randomized, open-label crossover study in healthy adults
    David J Greenblatt
    Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA 02111, USA
    Clin Ther 35:604-11. 2013
    ..A zolpidem sublingual tablet (ZST) formulation was recently approved by the US Food and Drug Administration to treat middle-of-the-night (MOTN) awakening with difficulty returning to sleep...
  52. doi request reprint Pharmacokinetic profile of SKP-1041, a modified release formulation of zaleplon
    David J Greenblatt
    Program in Pharmacology and Experimental Therapeutics, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA
    Biopharm Drug Dispos 32:489-97. 2011
    ..Two investigations aimed to define the pharmacokinetic profile of a modified-release preparation of zaleplon (SKP-1041)...
  53. ncbi request reprint Evaluation of 3'-azido-3'-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism
    Michael H Court
    Comparative and Molecular Pharmacogenetics Laboratory, Tufts University, Boston, MA 02111, USA
    Drug Metab Dispos 31:1125-33. 2003
    ..Codeine is not a useful UGT2B7 probe substrate because of significant glucuronidation by UGT2B4. The UGT2B7*2 polymorphism is not a determinant of glucuronidation of AZT, morphine, or codeine in HLMs...
  54. ncbi request reprint Induction of P-glycoprotein expression and activity by ritonavir in bovine brain microvessel endothelial cells
    Michael D Perloff
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharm Pharmacol 59:947-53. 2007
    ..Similar findings may occur at the clinical level with prolonged HIV protease inhibitor use, giving insight into the central nervous system as an HIV sanctuary site and eventual development of HIV dementia...
  55. ncbi request reprint Influence of fruit juices on drug disposition: discrepancies between in vitro and clinical studies
    Dora Farkas
    Tufts University School of Medicine, Department of Pharmacology and Experimental Therapeutics, Boston, MA 02111, USA
    Expert Opin Drug Metab Toxicol 4:381-93. 2008
    ..After the discovery of this interaction almost 20 years ago, there have been many reports investigating the effects of fruit juices on drug disposition...
  56. doi request reprint The absence of an interaction between warfarin and cranberry juice: a randomized, double-blind trial
    Jack Ansell
    Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
    J Clin Pharmacol 49:824-30. 2009
    ..Enhanced warfarin anticoagulation attributed to CJ in anecdotal reports may represent a chance temporal association...
  57. ncbi request reprint Microsomal protein concentration modifies the apparent inhibitory potency of CYP3A inhibitors
    Thanh Huu Tran
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and New England Medical Center, Boston, Massachusetts 02111, USA
    Drug Metab Dispos 30:1441-5. 2002
    ..The effect can be minimized by use of the lowest possible microsomal protein concentration for in vitro studies of metabolic inhibition...
  58. ncbi request reprint Fexofenadine transport in Caco-2 cells: inhibition with verapamil and ritonavir
    Michael D Perloff
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Clin Pharmacol 42:1269-74. 2002
    ..Thefindings support the use of FXD as an index or probe compound to reflect P-gp activity in vivo...
  59. doi request reprint Sources of variability in ketoconazole inhibition of human cytochrome P450 3A in vitro
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA
    Xenobiotica 40:713-20. 2010
    ....
  60. ncbi request reprint Evaluation of Supermix as an in vitro model of human liver microsomal drug metabolism
    Karthik Venkatakrishnan
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Biopharm Drug Dispos 23:183-90. 2002
    ..These factors should be considered when this formulation is used as an in vitro model in human liver microsomal drug metabolism studies...
  61. ncbi request reprint Interactions of tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen with P-glycoprotein and CYP3A
    Tanios S Bekaii-Saab
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    Biopharm Drug Dispos 25:283-9. 2004
    ..Tamoxifen, and possibly its metabolites, may have the potential to cause drug interactions by inhibiting both drug transport and metabolism. This possibility requires further evaluation in clinical studies...
  62. ncbi request reprint Inhibition of human cytochromes P450 by components of Ginkgo biloba
    Lisa L von Moltke
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharm Pharmacol 56:1039-44. 2004
    ..The clinical importance of these potential inhibitors will depend on their amounts in ginkgo preparations sold to the public, and the extent to which their bioavailability allows them to reach the CYP enzymes in-situ...
  63. ncbi request reprint The effect of age on P-glycoprotein expression and function in the Fischer-344 rat
    Jill S Warrington
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharmacol Exp Ther 309:730-6. 2004
    ..The converse pattern was observed in the kidney. Thus, age-related changes in P-gp expression and function are likely to be tissue-specific, and these changes may be inversely related to differences in CYP3A expression...
  64. ncbi request reprint Evaluation of 5-hydroxytryptophol and other endogenous serotonin (5-hydroxytryptamine) analogs as substrates for UDP-glucuronosyltransferase 1A6
    Soundararajan Krishnaswamy
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Drug Metab Dispos 32:862-9. 2004
    ..In conclusion, these results indicate that human UGT1A6 plays a predominant role in the glucuronidation of 5-hydroxytryptophol and N-acetylserotonin, whereas 6-hydroxymelatonin is not a substrate for this enzyme...
  65. ncbi request reprint Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: comparison with fluoxetine and quinidine
    Kirk M Bertelsen
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Drug Metab Dispos 31:289-93. 2003
    ..These data are consistent with mechanism-based inhibition of CYP2D6 by paroxetine but not by quinidine or fluoxetine...
  66. ncbi request reprint Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1A9
    Michael H Court
    Comparative and Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Drug Metab Dispos 30:1257-65. 2002
    ..Allelic variation associated with the UGT2B15 gene may explain polymorphic S-oxazepam glucuronidation in humans...
  67. ncbi request reprint Clinically important drug interactions with zopiclone, zolpidem and zaleplon
    Leah M Hesse
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    CNS Drugs 17:513-32. 2003
    ....
  68. doi request reprint Analysis of drug interactions involving fruit beverages and organic anion-transporting polypeptides
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA
    J Clin Pharmacol 49:1403-7. 2009
    ..Beyond these two examples, other meaningful drug interactions with fruit beverages via OATP inhibition are not established at the present time...
  69. ncbi request reprint In vitro biotransformation of sildenafil (Viagra) in the male rat: the role of CYP2C11
    Jill S Warrington
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts New England Medical Center, Boston, MA 02111, USA
    Drug Metab Dispos 30:655-7. 2002
    ..P450 isoforms mediating sildenafil biotransformation differ substantially between humans and the male rat, thereby limiting the applicability of this species as a model for sildenafil metabolism and drug interactions in humans...
  70. ncbi request reprint Human cytochromes mediating gepirone biotransformation at low substrate concentrations
    David J Greenblatt
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts New England Medical Center, Boston MA 02111, USA
    Biopharm Drug Dispos 24:87-94. 2003
    ..CYP2D6 would account for less than 5% of net clearance. The findings are consistent with previous in vitro studies of gepirone using higher substrate concentrations...
  71. ncbi request reprint Acute zolpidem administration produces pharmacodynamic and receptor occupancy changes at similar doses
    Jeanne M Fahey
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and the Division of Clinical Pharmacology, Tufts New England Medical Center, 136 Harrison Avenue, Boston, MA 02111, USA
    Pharmacol Biochem Behav 83:21-7. 2006
    ..In addition, zolpidem had no significant effect on the affinity of the benzodiazepine receptor for [3H]flunitrazepam, but did decrease the density of receptor binding sites...
  72. pmc The effect of grapefruit juice on drug disposition
    Michael J Hanley
    Tufts University School of Medicine, Program in Pharmacology and Experimental Therapeutics, 136 Harrison Avenue, Boston, MA 02111, USA
    Expert Opin Drug Metab Toxicol 7:267-86. 2011
    ..Although knowledge regarding the effects of GFJ on drug disposition continues to expand, the list of drugs studied in the clinical setting remains relatively limited...
  73. ncbi request reprint Zolpidem pharmacokinetic properties in young females: influence of smoking and oral contraceptive use
    Joel O Olubodun
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts New England Medical Center, Boston, MA 02111
    J Clin Pharmacol 42:1142-6. 2002
    ..In any case, the differences were quantitatively small and not likely to be of clinical importance...
  74. ncbi request reprint Effect of 7-day exposure to midazolam on electroencephalogram pharmacodynamics in rats: a model to study multiple pharmacokinetic-pharmacodynamic relationships in individual animals
    Bart E Laurijssens
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    J Pharm Pharmacol 54:77-86. 2002
    ..A modest degree of tolerance to midazolam was found with this paradigm, the effect only being evident after correction for the fraction unbound of midazolam...
  75. ncbi request reprint Identification of common polymorphisms in the promoter of the UGT1A9 gene: evidence that UGT1A9 protein and activity levels are strongly genetically controlled in the liver
    Hugo Girard
    Canada Research Chair in Pharmacogenomics, Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada
    Pharmacogenetics 14:501-15. 2004
    ..The great interindividual variability of UGT1A9-mediated glucuronidation remains poorly explained, while evidence for its genetic origin exists...
  76. ncbi request reprint Limited sampling strategy to predict AUC of the CYP3A phenotyping probe midazolam in adults: application to various assay techniques
    Jooran S Kim
    Clinical Pharmacology Research Center, Bassett Healthcare, Cooperstown, New York 13326 1394, USA
    J Clin Pharmacol 42:376-82. 2002
    ..A limited sampling strategy is more convenient and cost-effective than standard sampling strategies and is applicable to more than one assay technique...
  77. ncbi request reprint Interdose elevation in plasma cortisol during chronic treatment with alprazolam but not lorazepam in the elderly
    Nunzio Pomara
    Geriatric Psychiatry Program, Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
    Neuropsychopharmacology 29:605-11. 2004
    ..If confirmed, this effect may contribute to an increased risk for drug escalation and dependence during chronic alprazolam treatment...
  78. ncbi request reprint Apolipoprotein E epsilon4 allele and lorazepam effects on memory in high-functioning older adults
    Nunzio Pomara
    Geriatric Psychiatry Program, Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
    Arch Gen Psychiatry 62:209-16. 2005
    ..The apolipoprotein E (APOE) epsilon4 allele has been implicated as a significant risk factor in the development of late-onset Alzheimer disease, but the evidence of cognitive sequelae in healthy individuals has been mixed...
  79. ncbi request reprint Effects of acute lorazepam administration on aminergic activity in normal elderly subjects: relationship to performance effects and apolipoprotein genotype
    Nunzio Pomara
    Geriatric Psychiatry Program, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA
    Neurochem Res 29:1391-8. 2004
    ..The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance...
  80. ncbi request reprint Dose-dependent retrograde facilitation of verbal memory in healthy elderly after acute oral lorazepam administration
    Nunzio Pomara
    Geriatric Psychiatry Program, Nathan S Kline Institute, 140 Old Orangeburg Rd Bldg 35, Orangeburg, NY 10962, USA
    Psychopharmacology (Berl) 185:487-94. 2006
    ....
  81. ncbi request reprint UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver
    Hugo Girard
    Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, 2705 Boulevard Laurier, Quebec G1V 4G2, Canada
    Hepatology 42:448-57. 2005
    ..In conclusion, UGT1A1 polymorphisms modulate the hepatic metabolism of the carcinogenic intermediate of PhIP and may determine the level of its exposure and potentially influence the risk of cancer through dietary exposure to HCAs...
  82. ncbi request reprint Role of CYP3A and CYP2E1 in alcohol-mediated increases in acetaminophen hepatotoxicity: comparison of wild-type and Cyp2e1(-/-) mice
    Kristina K Wolf
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA
    Drug Metab Dispos 35:1223-31. 2007
    ..In conclusion, these findings suggest that both CYP3A and CYP2E1 contribute to APAP hepatotoxicity in alcohol-treated mice...
  83. ncbi request reprint Baseline plasma GABA: its relationship to the adverse effects of acute lorazepam administration on cognition in the elderly
    Nunzio Pomara
    Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
    Neurochem Res 29:2311-5. 2004
    ..Plasma GABA concentration does not appear to be a useful marker of susceptibility to benzodiazepine-induced cognitive toxicity in the elderly. Other approaches to estimating central GABA activity should be pursued...
  84. ncbi request reprint The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liver
    Hugo Girard
    Laboratory of Pharmacogenomics, Centre hospitalier de l Universite Laval, Quebec, QC, Canada G1V 4G2
    Drug Metab Dispos 34:1220-8. 2006
    ....
  85. ncbi request reprint Drug metabolism and drug interactions: application and clinical value of in vitro models
    Karthik Venkatakrishnan
    Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer Global Research and Development, Groton, CT, USA
    Curr Drug Metab 4:423-59. 2003
    ....
  86. ncbi request reprint Cortisol response to diazepam: its relationship to age, dose, duration of treatment, and presence of generalized anxiety disorder
    Nunzio Pomara
    Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Building 35, Orangeburg, NY 10962, USA
    Psychopharmacology (Berl) 178:1-8. 2005
    ..However, the effects of chronic diazepam treatment on cortisol have been less studied, and the relationship to age, anxiety, duration of treatment, and dose are not well understood...