Research Topics
Species | Paul WatkinsSummaryAffiliation: University of North Carolina Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Common allelic variants of cytochrome P4503A4 and their prevalence in different populationsJatinder K Lamba
Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
Pharmacogenetics 12:121-32. 2002..None of the 28 CYP3A4 SNPs identified in CYP3A4 phenotyped persons (most individuals being heterozygous for any CYP3A4 variant) was associated with low hepatic CYP3A4 protein expression or low CYP3A4 activity in vivo...- Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trialPaul B Watkins
Department of Medicine, University of North Carolina, Chapel Hill, USA
JAMA 296:87-93. 2006..During a clinical trial of a novel hydrocodone/acetaminophen combination, a high incidence of serum alanine aminotransferase (ALT) elevations was observed... - Drug safety sciences and the bottleneck in drug developmentP B Watkins
Hamner University of North Carolina, Institute for Drug Safety Sciences, Schools of Medicine and Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA
Clin Pharmacol Ther 89:788-90. 2011..If the drug is ultimately approved, this detour will result in costs and potential revenue loss to the sponsor of well over $1 billion... - Biomarkers for the diagnosis and management of drug-induced liver injuryPaul B Watkins
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Semin Liver Dis 29:393-9. 2009..Such discovery efforts will require the establishment of well-annotated serum and urine banks from prospective clinical trials of drugs capable of causing progressive liver injury... - Idiosyncratic liver injury: challenges and approachesPaul B Watkins
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Toxicol Pathol 33:1-5. 2005..This network should provide heretofore missing resources required to address the problem... - Clinical pattern of zileuton-associated liver injury: results of a 12-month study in patients with chronic asthmaPaul B Watkins
University of North Carolina Hospital, Chapel Hill, North Carolina 27599 7600, USA
Drug Saf 30:805-15. 2007..To more fully characterise the hepatic effects of zileuton, and to establish appropriate monitoring guidelines, a 12-month open-label, safety surveillance study was conducted prior to FDA approval... - Drug-induced liver injury: summary of a single topic clinical research conferencePaul B Watkins
University of North Carolina, Chapel Hill, NC, USA
Hepatology 43:618-31. 2006..The presentations spanned many different areas of DILI, and included novel data concerning mechanisms of hepatotoxicity, new "omics" approaches, and the challenges of improving causation assessment... - Evaluation of drug-induced serious hepatotoxicity (eDISH): application of this data organization approach to phase III clinical trials of rivaroxaban after total hip or knee replacement surgeryPaul B Watkins
Hamner UNC Institute for Drug Safety Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA
Drug Saf 34:243-52. 2011.... - Hepatic but not intestinal CYP3A4 displays dose-dependent induction by efavirenz in humansStephane Mouly
General Clinical Research Center, University of North Carolina, Chapel Hill 27599, USA
Clin Pharmacol Ther 72:1-9. 2002.... - Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5Stéphane 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... - A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interactionMary F Paine
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, NC, USA
Am J Clin Nutr 83:1097-105. 2006..4) h, respectively]. CONCLUSION: Furanocoumarins are the active ingredients in GFJ responsible for enhancing the systemic exposure of felodipine and probably other CYP3A4 substrates that undergo extensive intestinal first-pass metabolism... - Identification of a novel route of extraction of sirolimus in human small intestine: roles of metabolism and secretionMary 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.... - Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injuryBarbara A Wetmore
The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
Hepatology 51:2127-39. 2010..Further, the possibility of identifying chemical-specific transcriptional profiles from circulating mRNAs could open a range of possibilities for identifying the etiology of drug/chemical-induced liver injury... - 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... - Two major grapefruit juice components differ in time to onset of intestinal CYP3A4 inhibitionMary 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... - New insights into drug absorption: studies with sirolimusMary 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... - Two major grapefruit juice components differ in intestinal CYP3A4 inhibition kinetic and binding propertiesMary 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... - Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporineMary 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... - CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adultsRaymond C Givens
General Clinical Research Center, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA
J Appl Physiol 95:1297-300. 2003..3 mmHg. We speculate whether a high CYP3A5 expressor allele frequency among African-Americans may contribute to a high prevalence of sodium-sensitive hypertension in this population... - Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United StatesNaga Chalasani
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Gastroenterology 135:1924-34, 1934.e1-4. 2008..This report summarizes the causes, clinical features, and outcomes from the first 300 patients enrolled... - Contributions of CYP3A4, P-glycoprotein, and serum protein binding to the intestinal first-pass extraction of saquinavirStéphane 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... - Using controlled clinical trials to learn more about acute drug-induced liver injuryPaul B Watkins
Hamner Center for Drug Safety Sciences, University of North Carolina, Chapel Hill, NC, USA
Hepatology 48:1680-9. 2008.... - Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humansAlison H Harrill
Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Genome Res 19:1507-15. 2009..These studies demonstrate that a diverse mouse population can be used to understand and predict adverse toxicity in heterogeneous human populations through guided resequencing... - Acetaminophen dosing of humans results in blood transcriptome and metabolome changes consistent with impaired oxidative phosphorylationRick D Fannin
National Institute of Environmental Health Sciences Microarray Group, National Institutes of Health NIH, Research Triangle Park, NC 27709, USA
Hepatology 51:227-36. 2010..The timing of the changes and the correlation with NAPQI production are consistent with mechanisms known to underlie APAP hepatoxicity. These studies support the further exploration of the blood transcriptome for biomarkers of DILI... - Liver transplantation for acute liver failure from drug induced liver injury in the United StatesMark W Russo
Division of Gastroenterology and Hepatology, Department of Medicine and Center for Gastrointestinal Biology and Diseases, University of North Carolina, Chapel Hill, NC 27599 7080, USA
Liver Transpl 10:1018-23. 2004..The increased frequency of African-American women undergoing liver transplantation for non-APAP drug induced liver injury warrants further study... - Identifying genetic risk factors for serious adverse drug reactions: current progress and challengesRussell A Wilke
Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA
Nat Rev Drug Discov 6:904-16. 2007..Key challenges for the discovery of predictive risk alleles for these SADRs are also considered... - Differential inhibition of rat and human Na+-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1)by bosentan: a mechanism for species differences in hepatotoxicityElaine M Leslie
School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7360, USA
J Pharmacol Exp Ther 321:1170-8. 2007..In conclusion, differential inhibition of Ntcp and NTCP may represent a novel mechanism for species differences in bosentan-induced hepatotoxicity... - The Environmental Polymorphisms Registry: a DNA resource to study genetic susceptibility lociPatricia C Chulada
Clinical Research Program, National Institute of Environmental Health Sciences, 111 T W Alexander Drive, Research Triangle Park, NC 27709, USA
Hum Genet 123:207-14. 2008..The success of the EPR based on the number of subjects recruited and genetic studies underway, suggests that it will be a model for future DNA resources... - The influence of CYP3A5 expression on the extent of hepatic CYP3A inhibition is substrate-dependent: an in vitro-in vivo evaluationNina 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... - 6'7'-Dihydroxybergamottin contributes to the grapefruit juice effectShefali M Kakar
Department of Pharmacology, University of Michigan, Ann Arbor, USA
Clin Pharmacol Ther 75:569-79. 2004..CONCLUSION: The interaction between grapefruit juice serum and felodipine can be attributed largely to DHB. This establishes DHB as an important contributor to the grapefruit juice effect... - Insight into hepatotoxicity: The troglitazone experiencePaul B Watkins
Hepatology 41:229-30. 2005 - Intestinal and hepatic CYP3A4 catalyze hydroxylation of 1alpha,25-dihydroxyvitamin D(3): implications for drug-induced osteomalaciaYang Xu
Department of Pharmaceutics, Box 357610, University of Washington, Seattle, WA 98195-7610, USA
Mol Pharmacol 69:56-65. 2006..These and other data suggest that induction of CYP3A4-dependent 1,25(OH)(2)D(3) metabolism by antiepileptic drugs and other PXR ligands may diminish intestinal effects of the hormone and contribute to osteomalacia... - Did this drug cause my patient's hepatitis?Neil Kaplowitz
Ann Intern Med 138:159-60; author reply 159-60. 2003 - 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... - Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interactionWei C Lau
Department of Anesthesiology, University of Michigan, Ann Arbor, USA
Circulation 107:32-7. 2003..Because atorvastatin is metabolized by cytochrome P450 (CYP) 3A4, we hypothesized that clopidogrel might be activated by CYP3A4... - Cytochrome P450 3A4 and P-glycoprotein mediate the interaction between an oral erythromycin breath test and rifampinMary F Paine
Department of Pharmacology, University of Michigan, Ann Arbor, USA
Clin Pharmacol Ther 72:524-35. 2002..The erythromycin-rifampin interaction cannot be attributed to CYP3A4 induction alone and probably also reflected intestinal P-glycoprotein induction... - Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistanceWei C Lau
Department of Anesthesiology, University of Michigan Health System, 1G323 University Hospital, Box 0048, 1500 East Medical Center Drive, Ann Arbor, MI 48109 0048, USA
Circulation 109:166-71. 2004..Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity... - Role of cytochrome P450 phenotyping in cancer treatmentE Claire Dees
J Clin Oncol 23:1053-5. 2005 - Increased CYP3A4 copy number in TONG/HCC cells but not in DNA from other humansJatinder K Lamba
Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA
Pharmacogenet Genomics 16:415-27. 2006..Tumors with increased CYP3A copy number (via amplification or increased chromosome 7q) would be expected to show reduced cytotoxicity to some chemotherapeutic drugs and potentially an increase in the outgrowth of drug resistant tumors... - Are patients with elevated liver tests at increased risk of drug-induced liver injury?Mark W Russo
Gastroenterology 126:1477-80. 2004 - Drug-induced liver injury networkPaul B Watkins
Am J Gastroenterol 103:1574-5. 2008 - CYP3A probes can quantitatively predict the in vivo kinetics of other CYP3A substrates and can accurately assess CYP3A induction and inhibitionEvan D Kharasch
University of Washington School of Medicine, Seattle, WA 98195, USA
Mol Interv 5:151-3. 2005..Recently, Benet has written on the futility of such an enterprise; however, other researchers believe the identification of valuable predictive probes is not only possible but crucial... - Tolcapone: an efficacy and safety review (2007)C Warren Olanow
Department of Neurology, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029, USA
Clin Neuropharmacol 30:287-94. 2007..In addition, patients must be taken off the drug if blood tests show enzyme elevation of greater than twice the upper limit of normal. This article reviews the data pertaining to the safety and efficacy of tolcapone... - MDR1 genotype is associated with hepatic cytochrome P450 3A4 basal and induction phenotypeJatinder Lamba
Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA
Clin Pharmacol Ther 79:325-38. 2006..Moreover, the influence of MDR1 genotype on CYP3A4 expression adds additional complexity to determining the relative contribution of the MDR1 alleles to the disposition of substrates shared by CYP3A4 and MDR1/P-glycoprotein... - Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalaciaChangcheng Zhou
Department of Pharmaceutics, University of Washington, Seattle, Washington 98195 7610, USA
J Clin Invest 116:1703-12. 2006.... - Growth hormone secretion pattern is an independent regulator of growth hormone actions in humansCraig A Jaffe
Divisions of Endocrinology and Metabolism, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
Am J Physiol Endocrinol Metab 283:E1008-15. 2002..Gender differences in drug metabolism and, potentially, gender differences in growth rate may be explained by sex-specific GH secretion patterns...
Research Grants
- Hepatoxicity Clincal Research NetworkPaul Watkins; Fiscal Year: 2007..We anticipate that our proposed infrastructure will allow successful identification and enrollment of patients experiencing severe DILl within the mid-Atlantic region of the country. ..
- FURANOCOUMARINS AND DRUGS EFFECT ON CYP3A4Paul Watkins; Fiscal Year: 2007..abstract_text> ..
- GENERAL CLINICAL RESEARCH CENTERS ANNUAL MEETINGPaul Watkins; Fiscal Year: 2006..abstract_text> ..