M F Paine

Summary

Affiliation: University of North Carolina
Country: USA

Publications

  1. ncbi request reprint Two major grapefruit juice components differ in intestinal CYP3A4 inhibition kinetic and binding properties
    Mary F Paine
    General Clinical Research Center, Room 3005 Bldg APCF, CB 7600, UNC Hospitals, Chapel Hill, NC 27599 7600, USA
    Drug Metab Dispos 32:1146-53. 2004
  2. ncbi request reprint Two major grapefruit juice components differ in time to onset of intestinal CYP3A4 inhibition
    Mary F Paine
    General Clinical Research Center, Room 3005 Bldg APCF, CB 7600, UNC Hospitals, Chapel Hill, NC 27599 7600, USA
    J Pharmacol Exp Ther 312:1151-60. 2005
  3. pmc The human intestinal cytochrome P450 "pie"
    Mary F Paine
    General Clinical Research Center, Room 3005 Bldg APCF, CB 7600, UNC Hospitals, Chapel Hill, NC 27599 7600, USA
    Drug Metab Dispos 34:880-6. 2006
  4. ncbi request reprint A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction
    Mary F Paine
    Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, NC, USA
    Am J Clin Nutr 83:1097-105. 2006
  5. ncbi request reprint Can oral midazolam predict oral cyclosporine disposition?
    M F Paine
    Department of Pharmaceutics, University of Washington, Seattle, WA, USA
    Eur J Pharm Sci 12:51-62. 2000
  6. ncbi request reprint Do men and women differ in proximal small intestinal CYP3A or P-glycoprotein expression?
    Mary F Paine
    General Clinical Research Center, Room 3005, Bldg APCF, CB 7600, UNC Hospitals, Chapel Hill, NC 27599 7600, USA
    Drug Metab Dispos 33:426-33. 2005
  7. ncbi request reprint New insights into drug absorption: studies with sirolimus
    Mary F Paine
    General Clinical Research Center and Division of Pharmacotherapy, University of North Carolina, Chapel Hill, North Carolina 27599 7600, USA
    Ther Drug Monit 26:463-7. 2004
  8. ncbi request reprint Clinical relevance of the small intestine as an organ of drug elimination: drug-fruit juice interactions
    Mary F Paine
    University of North Carolina, School of Pharmacy, 3324 Kerr Hall, CB 7360, Chapel Hill, NC 27599 7360, USA
    Expert Opin Drug Metab Toxicol 3:67-80. 2007
  9. ncbi request reprint Identification of a novel route of extraction of sirolimus in human small intestine: roles of metabolism and secretion
    Mary F Paine
    General Clinical Research Center and Division of Pharmacotherapy, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Pharmacol Exp Ther 301:174-86. 2002
  10. ncbi request reprint Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5
    Stéphane J Mouly
    General Clinical Research Center, School of Pharmacy, and Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    Clin Pharmacol Ther 78:605-18. 2005

Research Grants

Collaborators

Detail Information

Publications24

  1. ncbi request reprint Two major grapefruit juice components differ in intestinal CYP3A4 inhibition kinetic and binding properties
    Mary F Paine
    General Clinical Research Center, Room 3005 Bldg APCF, CB 7600, UNC Hospitals, Chapel Hill, NC 27599 7600, USA
    Drug Metab Dispos 32:1146-53. 2004
    ..Results also emphasize the importance of appropriate substrate selection when designing inhibition studies involving dietary constituents...
  2. ncbi request reprint Two major grapefruit juice components differ in time to onset of intestinal CYP3A4 inhibition
    Mary F Paine
    General Clinical Research Center, Room 3005 Bldg APCF, CB 7600, UNC Hospitals, Chapel Hill, NC 27599 7600, USA
    J Pharmacol Exp Ther 312:1151-60. 2005
    ..However, foods containing BG but not DHB (e.g., lime juice) could produce a substrate-dependent interaction with drugs consumed concomitantly, but a substrate-independent interaction with drugs taken several hours after food consumption...
  3. pmc The human intestinal cytochrome P450 "pie"
    Mary F Paine
    General Clinical Research Center, Room 3005 Bldg APCF, CB 7600, UNC Hospitals, Chapel Hill, NC 27599 7600, USA
    Drug Metab Dispos 34:880-6. 2006
    ..On average, CYP3A and CYP2C9 represents the major pieces of the intestinal P450 pie, accounting for 80 and 15%, respectively, of total immunoquantified P450s...
  4. ncbi request reprint A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction
    Mary F Paine
    Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, NC, USA
    Am J Clin Nutr 83:1097-105. 2006
    ..Furanocoumarins have been identified as major CYP3A4 inhibitors contained in the juice, but their contribution to the GFJ effect in vivo remains unclear...
  5. ncbi request reprint Can oral midazolam predict oral cyclosporine disposition?
    M F Paine
    Department of Pharmaceutics, University of Washington, Seattle, WA, USA
    Eur J Pharm Sci 12:51-62. 2000
    ..We conclude that although oral midazolam is unlikely to be clinically useful as a probe for cyclosporine disposition, its utility in the prediction of other orally administered CYP3A substrates cannot be out ruled...
  6. ncbi request reprint Do men and women differ in proximal small intestinal CYP3A or P-glycoprotein expression?
    Mary F Paine
    General Clinical Research Center, Room 3005, Bldg APCF, CB 7600, UNC Hospitals, Chapel Hill, NC 27599 7600, USA
    Drug Metab Dispos 33:426-33. 2005
    ..Ramifications of lower intestinal CYP3A4 content in post- versus premenopausal women require further investigation...
  7. ncbi request reprint New insights into drug absorption: studies with sirolimus
    Mary F Paine
    General Clinical Research Center and Division of Pharmacotherapy, University of North Carolina, Chapel Hill, North Carolina 27599 7600, USA
    Ther Drug Monit 26:463-7. 2004
    ..This new insight into the intestinal elimination of sirolimus, which was not identified using traditional drug metabolism/transport screening methods, may represent another source for the limited absorption of sirolimus...
  8. ncbi request reprint Clinical relevance of the small intestine as an organ of drug elimination: drug-fruit juice interactions
    Mary F Paine
    University of North Carolina, School of Pharmacy, 3324 Kerr Hall, CB 7360, Chapel Hill, NC 27599 7360, USA
    Expert Opin Drug Metab Toxicol 3:67-80. 2007
    ..Such an approach would allow proper between-study comparisons, and ultimately provide conclusive information as to whether specific dietary substances can be taken safely with certain medications...
  9. ncbi request reprint Identification of a novel route of extraction of sirolimus in human small intestine: roles of metabolism and secretion
    Mary F Paine
    General Clinical Research Center and Division of Pharmacotherapy, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Pharmacol Exp Ther 301:174-86. 2002
    ....
  10. ncbi request reprint Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5
    Stéphane J Mouly
    General Clinical Research Center, School of Pharmacy, and Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    Clin Pharmacol Ther 78:605-18. 2005
    ..The polymorphic CYP3A5 has also been shown to influence the saquinavir metabolite/parent urinary ratio, suggesting a role for CYP3A5...
  11. pmc Human enteric microsomal CYP4F enzymes O-demethylate the antiparasitic prodrug pafuramidine
    Michael Zhuo Wang
    School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Drug Metab Dispos 35:2067-75. 2007
    ..We conclude that enteric CYP4F enzymes could play a role in the first-pass biotransformation of DB289 and other xenobiotics...
  12. ncbi request reprint Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporine
    Mary F Paine
    School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 7360, USA
    Am J Clin Nutr 87:863-71. 2008
    ..It remains unclear whether furanocoumarins mediate drug-GFJ interactions involving CYP3A4 substrates that are also P-glycoprotein substrates...
  13. doi request reprint A gel-free MS-based quantitative proteomic approach accurately measures cytochrome P450 protein concentrations in human liver microsomes
    Michael Zhuo Wang
    School of Pharmacy, The University of North Carolina at Chapel Hill, NC 27599, USA
    Proteomics 8:4186-96. 2008
    ....
  14. doi request reprint Evidence of CYP3A allosterism in vivo: analysis of interaction between fluconazole and midazolam
    J Yang
    Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
    Clin Pharmacol Ther 91:442-9. 2012
    ..The 1'-OH-MDZ/4-OH-MDZ ratio may serve as a biomarker of such interactions among MDZ, CYP3A4/5, and other putative effectors...
  15. pmc Identification of a cranberry juice product that inhibits enteric CYP3A-mediated first-pass metabolism in humans
    Ngoc Ngo
    Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 7360, USA
    Drug Metab Dispos 37:514-22. 2009
    ....
  16. 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...
  17. ncbi request reprint Contributions of CYP3A4, P-glycoprotein, and serum protein binding to the intestinal first-pass extraction of saquinavir
    Stéphane J Mouly
    General Clinical Research Center, University of North Carolina Hospitals, Chapel Hill, NC 27599 7600, USA
    J Pharmacol Exp Ther 308:941-8. 2004
    ..We conclude that variable intestinal first-pass extraction of saquinavir in human immunodeficiency virus-infected patients could reflect variation in P-gp-mediated efflux and/or CYP3A4-catalyzed metabolism, but not in blood AAG levels...
  18. pmc CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O-demethylation of the antiparasitic prodrug DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime]
    Michael Zhuo Wang
    Division of Molecular Pharmaceutics, School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Drug Metab Dispos 34:1985-94. 2006
    ..g., CYP4F2, CYP4F3B) are the major enzymes responsible for M1 formation by HLMs. These findings indicate that, in human liver, members of the CYP4F subfamily biotransform not only endogenous compounds but also xenobiotics...
  19. pmc Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations
    Scott J Brantley
    Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 7569, USA
    J Pharmacol Exp Ther 332:1081-7. 2010
    ..These observations, combined with the high systemic silibinin concentrations (>5-75 microM) achieved in a phase I study involving prostate cancer patients, prompt clinical evaluation of a potential warfarin-milk thistle interaction...
  20. ncbi request reprint P-glycoprotein increases from proximal to distal regions of human small intestine
    Stephane Mouly
    Hopital Lariboisiere, Service de Medecine Interne A, 75475 Paris Cedex 10, France
    Pharm Res 20:1595-9. 2003
    ..Accordingly, the distribution of P-gp was examined along the entire length of the human small intestine...
  21. pmc Is quinine a suitable probe to assess the hepatic drug-metabolizing enzyme CYP3A4?
    Sompon Wanwimolruk
    College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA
    Br J Clin Pharmacol 54:643-51. 2002
    ..To evaluate the antimalarial agent quinine as a potential in vivo probe for hepatic cytochrome P450 (CYP) 3A4 activity...
  22. ncbi request reprint Cytochrome P450 3A4 and P-glycoprotein mediate the interaction between an oral erythromycin breath test and rifampin
    Mary F Paine
    Department of Pharmacology, University of Michigan, Ann Arbor, USA
    Clin Pharmacol Ther 72:524-35. 2002
    ..Accordingly, we evaluated an oral stable-labeled ((13)C) formulation of the test (ERMBT(oral)) as an alternative CYP3A4 phenotyping probe...
  23. ncbi request reprint 6'7'-Dihydroxybergamottin contributes to the grapefruit juice effect
    Shefali M Kakar
    Department of Pharmacology, University of Michigan, Ann Arbor, USA
    Clin Pharmacol Ther 75:569-79. 2004
    ..Our objective was to assess the contribution of 6',7'-dihydroxybergamottin (DHB) to the inhibitory effect of grapefruit juice toward intestinal cytochrome P450 (CYP) 3A4...
  24. ncbi request reprint A higher dose requirement of tacrolimus in active Crohn's disease may be related to a high intestinal P-glycoprotein content
    Alan L Buchman
    Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Dig Dis Sci 50:2312-5. 2005
    ..Elevated intestinal P-gp could have resulted in decreased tacrolimus absorption, thereby leading to decreased blood concentration and decreased efficacy in this patient. The cause and prevalence of this phenomenon are unknown...

Research Grants1

  1. Mechanisms Underlying Drug-Diet Interactions
    MARY PAINE; Fiscal Year: 2007
    ..The knowledge gained will provide critical information to both clinicians and the lay public as to whether specific dietary substances can be taken safely with certain medications. ..