Kathleen M Knights

Summary

Affiliation: Flinders University
Country: Australia

Publications

  1. doi request reprint Renal UDP-glucuronosyltransferases and the glucuronidation of xenobiotics and endogenous mediators
    Kathleen M Knights
    Department of Clinical Pharmacology, Flinders University, School of Medicine, Adelaide, Australia
    Drug Metab Rev 42:63-73. 2010
  2. ncbi request reprint Novel mechanisms of nonsteroidal anti-inflammatory drug-induced renal toxicity
    Kathleen M Knights
    Flinders University and Flinders Medical Centre, Department of Clinical Pharmacology, Bedford Park, Adelaide 5042, Australia
    Expert Opin Drug Metab Toxicol 1:399-408. 2005
  3. pmc Non-selective nonsteroidal anti-inflammatory drugs and cardiovascular events: is aldosterone the silent partner in crime?
    Kathleen M Knights
    Department of Clinical Pharmacology, Flinders University, Bedford Park, Adelaide, Australia
    Br J Clin Pharmacol 61:738-40. 2006
  4. pmc Aldosterone glucuronidation by human liver and kidney microsomes and recombinant UDP-glucuronosyltransferases: inhibition by NSAIDs
    Kathleen M Knights
    Department of Clinical Pharmacology, Flinders University, School of Medicine, Bedford Park, Adelaide 5042, Australia
    Br J Clin Pharmacol 68:402-12. 2009
  5. ncbi request reprint Xenobiotic-CoA ligases: kinetic and molecular characterization
    K M Knights
    Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Flinders University, Bedford Park, Adelaide 5042, Australia
    Curr Drug Metab 1:49-66. 2000
  6. ncbi request reprint In vitro metabolism of acitretin by human liver microsomes: evidence of an acitretinoyl-coenzyme A thioester conjugate in the transesterification to etretinate
    K M Knights
    Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Flinders University, 5042, Adelaide, Australia
    Biochem Pharmacol 60:507-16. 2000
  7. doi request reprint Spironolactone and canrenone inhibit UGT2B7-catalyzed human liver and kidney microsomal aldosterone 18beta-glucuronidation: a potential drug interaction
    Kathleen M Knights
    Department of Clinical Pharmacology, Flinders University School of Medicine, Adelaide, Australia
    Drug Metab Dispos 38:1011-4. 2010
  8. ncbi request reprint Role of hepatic fatty acid:coenzyme A ligases in the metabolism of xenobiotic carboxylic acids
    K M Knights
    Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Flinders University of South Australia, Australia
    Clin Exp Pharmacol Physiol 25:776-82. 1998
  9. ncbi request reprint Amino acid conjugation: contribution to the metabolism and toxicity of xenobiotic carboxylic acids
    Kathleen M Knights
    Flinders University and Flinders Medical Center, Department of Clinical Pharmacology, Bedford Park, Adelaide 5042, Australia
    Expert Opin Drug Metab Toxicol 3:159-68. 2007
  10. doi request reprint The "albumin effect" and drug glucuronidation: bovine serum albumin and fatty acid-free human serum albumin enhance the glucuronidation of UDP-glucuronosyltransferase (UGT) 1A9 substrates but not UGT1A1 and UGT1A6 activities
    Andrew Rowland
    Department of Clinical Pharmacology, Flinders Medical Centre, Bedford Park, SA 5042, Australia
    Drug Metab Dispos 36:1056-62. 2008

Collaborators

Detail Information

Publications30

  1. doi request reprint Renal UDP-glucuronosyltransferases and the glucuronidation of xenobiotics and endogenous mediators
    Kathleen M Knights
    Department of Clinical Pharmacology, Flinders University, School of Medicine, Adelaide, Australia
    Drug Metab Rev 42:63-73. 2010
    ....
  2. ncbi request reprint Novel mechanisms of nonsteroidal anti-inflammatory drug-induced renal toxicity
    Kathleen M Knights
    Flinders University and Flinders Medical Centre, Department of Clinical Pharmacology, Bedford Park, Adelaide 5042, Australia
    Expert Opin Drug Metab Toxicol 1:399-408. 2005
    ..The common involvement of UGT in the metabolism of arachidonic acid, eicosanoids and NSAIDs is discussed in the context of novel mechanisms of NSAID-induced nephrotoxicity...
  3. pmc Non-selective nonsteroidal anti-inflammatory drugs and cardiovascular events: is aldosterone the silent partner in crime?
    Kathleen M Knights
    Department of Clinical Pharmacology, Flinders University, Bedford Park, Adelaide, Australia
    Br J Clin Pharmacol 61:738-40. 2006
    ..The question remains whether inhibition of aldosterone metabolism by non-selective NSAIDs is a casual or causal factor in NSAID-induced cardiovascular toxicity...
  4. pmc Aldosterone glucuronidation by human liver and kidney microsomes and recombinant UDP-glucuronosyltransferases: inhibition by NSAIDs
    Kathleen M Knights
    Department of Clinical Pharmacology, Flinders University, School of Medicine, Bedford Park, Adelaide 5042, Australia
    Br J Clin Pharmacol 68:402-12. 2009
    ....
  5. ncbi request reprint Xenobiotic-CoA ligases: kinetic and molecular characterization
    K M Knights
    Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Flinders University, Bedford Park, Adelaide 5042, Australia
    Curr Drug Metab 1:49-66. 2000
    ....
  6. ncbi request reprint In vitro metabolism of acitretin by human liver microsomes: evidence of an acitretinoyl-coenzyme A thioester conjugate in the transesterification to etretinate
    K M Knights
    Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Flinders University, 5042, Adelaide, Australia
    Biochem Pharmacol 60:507-16. 2000
    ..Predicting clearance of acitretin in vivo via this unique metabolic pathway will be a challenge, as the intracellular concentration of ethanol could never be predicted with any degree of accuracy in humans...
  7. doi request reprint Spironolactone and canrenone inhibit UGT2B7-catalyzed human liver and kidney microsomal aldosterone 18beta-glucuronidation: a potential drug interaction
    Kathleen M Knights
    Department of Clinical Pharmacology, Flinders University School of Medicine, Adelaide, Australia
    Drug Metab Dispos 38:1011-4. 2010
    ....
  8. ncbi request reprint Role of hepatic fatty acid:coenzyme A ligases in the metabolism of xenobiotic carboxylic acids
    K M Knights
    Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Flinders University of South Australia, Australia
    Clin Exp Pharmacol Physiol 25:776-82. 1998
    ..5. Continued characterization of the human xenobiotic-CoA ligases in terms of substrate/inhibitor profiles and regulation, will allow a greater understanding of the role of these enzymes in the metabolism of carboxylic acids...
  9. ncbi request reprint Amino acid conjugation: contribution to the metabolism and toxicity of xenobiotic carboxylic acids
    Kathleen M Knights
    Flinders University and Flinders Medical Center, Department of Clinical Pharmacology, Bedford Park, Adelaide 5042, Australia
    Expert Opin Drug Metab Toxicol 3:159-68. 2007
    ..This review discusses literature on the enzymes involved and the concept that xenobiotic substrate selectivity provides a barrier to protect the metabolic integrity of the mitochondria...
  10. doi request reprint The "albumin effect" and drug glucuronidation: bovine serum albumin and fatty acid-free human serum albumin enhance the glucuronidation of UDP-glucuronosyltransferase (UGT) 1A9 substrates but not UGT1A1 and UGT1A6 activities
    Andrew Rowland
    Department of Clinical Pharmacology, Flinders Medical Centre, Bedford Park, SA 5042, Australia
    Drug Metab Dispos 36:1056-62. 2008
    ..Only BSA caused a similar effect on 4MU glucuronidation by UGT1A1. It is concluded that BSA and HSAFAF reduce the K(m) values of only those enzymes inhibited by long-chain unsaturated fatty acids...
  11. doi request reprint Characterization of the binding of drugs to human intestinal fatty acid binding protein (IFABP): potential role of IFABP as an alternative to albumin for in vitro-in vivo extrapolation of drug kinetic parameters
    Andrew Rowland
    Department of Clinical Pharmacology, Flinders University School of Medicine, Flinders Medical Centre, Bedford Park, SA 5042, Australia
    Drug Metab Dispos 37:1395-403. 2009
    ..5 versus 1-1.5% for BSA) was necessary for a 10-fold reduction in this parameter. The results indicate that IFABP is likely to have advantages over BSA in microsomal kinetic studies with drugs that bind extensively to albumin...
  12. ncbi request reprint Binding of inhibitory fatty acids is responsible for the enhancement of UDP-glucuronosyltransferase 2B7 activity by albumin: implications for in vitro-in vivo extrapolation
    Andrew Rowland
    Department of Clinical Pharmacology, Flinders Medical Centre, Bedford Park, SA 5042, Australia
    J Pharmacol Exp Ther 321:137-47. 2007
    ..It is postulated that BSA and HSA-FAF sequester inhibitory fatty acids released during incubations, and the apparent high Km values observed for UGT2B7 substrates arise from the presence of these endogenous inhibitors...
  13. doi request reprint The prediction of drug-glucuronidation parameters in humans: UDP-glucuronosyltransferase enzyme-selective substrate and inhibitor probes for reaction phenotyping and in vitro-in vivo extrapolation of drug clearance and drug-drug interaction potential
    John O Miners
    Department of Clinical Pharmacology, Flinders University School of Medicine, Adelaide, Australia
    Drug Metab Rev 42:196-208. 2010
    ..Additionally, in vitro experimental approaches and scaling strategies have been successfully applied to the quantitative prediction of in vivo clearance via glucuronidation and drug-drug interaction potential...
  14. pmc Use of non-steroidal anti-inflammatory drugs and risk of incident myocardial infarction and heart failure, and all-cause mortality in the Australian veteran community
    Arduino A Mangoni
    Department of Clinical Pharmacology, School of Medicine, Flinders University, Australia
    Br J Clin Pharmacol 69:689-700. 2010
    ..We studied the association between either non-selective NSAIDs (ns-NSAIDs), selective COX-2 inhibitors, or any NSAID and risk of incident myocardial infarction (MI) and heart failure (HF), and all-cause mortality in elderly subjects...
  15. ncbi request reprint Glucuronidation of fenamates: kinetic studies using human kidney cortical microsomes and recombinant UDP-glucuronosyltransferase (UGT) 1A9 and 2B7
    Paraskevi Gaganis
    Department of Clinical Pharmacology, Flinders University and Flinders Medical Centre, Bedford Park, Adelaide, Australia
    Biochem Pharmacol 73:1683-91. 2007
    ..These data suggest that inhibitory metabolic interactions may occur between fenamates and other substrates metabolised by UGT2B7 and UGT1A9 in human kidney...
  16. doi request reprint Characterization of niflumic acid as a selective inhibitor of human liver microsomal UDP-glucuronosyltransferase 1A9: application to the reaction phenotyping of acetaminophen glucuronidation
    John O Miners
    Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia
    Drug Metab Dispos 39:644-52. 2011
    ..Mean K(m) values decreased in parallel with V(max), although the magnitude of the decrease was smaller. Taken together, the NFA inhibition data suggest that UGT1A6 is the major enzyme involved in APAP glucuronidation...
  17. ncbi request reprint Human renal cortical and medullary UDP-glucuronosyltransferases (UGTs): immunohistochemical localization of UGT2B7 and UGT1A enzymes and kinetic characterization of S-naproxen glucuronidation
    Paraskevi Gaganis
    Department of Clinical Pharmacology, Flinders University, Adelaide, Australia
    J Pharmacol Exp Ther 323:422-30. 2007
    ....
  18. doi request reprint The "albumin effect" and in vitro-in vivo extrapolation: sequestration of long-chain unsaturated fatty acids enhances phenytoin hydroxylation by human liver microsomal and recombinant cytochrome P450 2C9
    Andrew Rowland
    Department of Clinical Pharmacology, Flinders Medical Centre, Bedford Park, SA 5042, Australia
    Drug Metab Dispos 36:870-7. 2008
    ..The results indicate that previously determined in vitro K(m) values for CYP2C9 substrates are almost certainly overestimates, and accurate in vitro-in vivo extrapolation of kinetic data for CYP2C9 substrates is achievable...
  19. doi request reprint In vitro characterisation of human renal and hepatic frusemide glucuronidation and identification of the UDP-glucuronosyltransferase enzymes involved in this pathway
    Oranun Kerdpin
    Department of Clinical Pharmacology, Flinders University, Adelaide, Australia
    Biochem Pharmacol 76:249-57. 2008
    ..The data further demonstrate the potential importance of both the medulla and cortex in renal drug metabolism and detoxification...
  20. ncbi request reprint In vitro-in vivo correlation for drugs and other compounds eliminated by glucuronidation in humans: pitfalls and promises
    John O Miners
    Department of Clinical Pharmacology, Flinders University and Flinders Medical Centre, Adelaide, Australia
    Biochem Pharmacol 71:1531-9. 2006
    ....
  21. ncbi request reprint Evidence that unsaturated fatty acids are potent inhibitors of renal UDP-glucuronosyltransferases (UGT): kinetic studies using human kidney cortical microsomes and recombinant UGT1A9 and UGT2B7
    Paraskevi Tsoutsikos
    Department of Clinical Pharmacology, Flinders University and Flinders Medical Centre, Bedford Park, 5042, Adelaide, Australia
    Biochem Pharmacol 67:191-9. 2004
    ..It is conceivable therefore that during periods of renal ischaemia FA may impair renal drug glucuronidation thus compromising the protective capacity of the kidney against drug-induced nephrotoxicity...
  22. ncbi request reprint Inhibition of rat peroxisomal palmitoyl-CoA ligase by xenobiotic carboxylic acids
    B J Roberts
    Department of Clinical Pharmacology, Flinders University of South Australia, Adelaide
    Biochem Pharmacol 44:261-7. 1992
    ..The toxicological ramifications of peroxisomally mediated xenobiotic-CoA formation and the identification of other peroxisomal xenobiotic-CoA ligase(s) remain to be elucidated...
  23. ncbi request reprint Xenobiotic acyl-CoA formation: evidence of kinetically distinct hepatic microsomal long-chain fatty acid and nafenopin-CoA ligases
    K M Knights
    Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park
    Chem Biol Interact 90:215-23. 1994
    ....
  24. pmc S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen
    Kushari Bowalgaha
    Department of Clinical Pharmacology, Flinders University and Flinders Medical Centre, Bedford Park, Adelaide, Australia
    Br J Clin Pharmacol 60:423-33. 2005
    ..To characterize the kinetics of S-naproxen ('naproxen') acyl glucuronidation and desmethylnaproxen acyl and phenolic glucuronidation by human liver microsomes and identify the human UGT isoform(s) catalysing these reactions...
  25. ncbi request reprint In vitro covalent binding of nafenopin-CoA to human liver proteins
    B C Sallustio
    Department of Clinical Pharmacology, The Queen Elizabeth Hospital, Woodville, South Australia, 5011, Australia
    Toxicol Appl Pharmacol 163:176-82. 2000
    ..The ability of xenobiotics to acylate tissue proteins may have important biological consequences including perturbation of endogenous regulation of protein localization and function...
  26. ncbi request reprint Nafenopin-, ciprofibroyl-, and palmitoyl-CoA conjugation in vitro: kinetic and molecular characterization of marmoset liver microsomes and expressed MLCL1
    C J Drogemuller
    Department of Clinical Pharmacology, School of Medicine, Adelaide, 5042, Australia
    Arch Biochem Biophys 396:56-64. 2001
    ..More extensive characterization of the substrate specificity of marmoset LCL isoforms will aid in determining further the suitability of marmosets as a model for human xenobiotic metabolism via acyl-CoA conjugation...
  27. doi request reprint Use of non-steroidal anti-inflammatory drugs and risk of ischemic and hemorrhagic stroke in the Australian veteran community
    Arduino A Mangoni
    Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia
    Pharmacoepidemiol Drug Saf 19:490-8. 2010
    ..We studied the association between the use of non-selective ns-NSAIDs, selective COX-2 inhibitors, or either of these NSAIDs, and the incidence of stroke-related hospitalization in elderly subjects...
  28. ncbi request reprint Defining the COX inhibitor selectivity of NSAIDs: implications for understanding toxicity
    Kathleen M Knights
    Department of Clinical Pharmacology, Flinders University, Bedford Park, Adelaide, 5042 Australia
    Expert Rev Clin Pharmacol 3:769-76. 2010
    ..Data derived from in vitro models used to generate NSAID IC(50) values are discussed in the context of the difficulties in defining COX selectivity and hence understanding the toxicity of NSAIDs in current clinical use...
  29. ncbi request reprint The stereospecific incorporation of fenoprofen into rat hepatocyte and adipocyte triacylglycerols
    B C Sallustio
    Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park
    Biochem Pharmacol 37:1919-23. 1988
    ..However, this process (Km = 3780 microM) occurred at concentrations much higher than those found in man with usual doses...
  30. ncbi request reprint The glucuronidation of Delta4-3-Keto C19- and C21-hydroxysteroids by human liver microsomal and recombinant UDP-glucuronosyltransferases (UGTs): 6alpha- and 21-hydroxyprogesterone are selective substrates for UGT2B7
    K Bowalgaha
    Department of Clinical Pharmacology, Flinders Medical Centre, Bedford Park, SA 5042, Australia
    Drug Metab Dispos 35:363-70. 2007
    ....