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Xenobiotica
the fate of foreign compounds in biological systems
Volume 41, 2011 - Issue 2
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General Xenobiochemistry

Comparison of intrinsic clearances in human liver microsomes and suspended hepatocytes from the same donor livers: clearance-dependent relationship and implications for prediction of in vivo clearance

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Pages 124-136 | Received 10 Aug 2010, Accepted 06 Oct 2010, Published online: 09 Nov 2010

References

  • Baker M, Parton T. (2007). Kinetic determinants of hepatic clearance: plasma protein binding and hepatic uptake. Xenobiotica 37:1110–1134.
  • Barter ZE, Bayliss MK, Beaune PH, Boobis AR, Carlile DJ, Edwards RJ, Houston JB, Lake BG, Lipscomb JC, Pelkonen OR, Tucker GT, Rostami-Hodjegan A. (2007). Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liver. Curr Drug Metab 8:33–45.
  • Brown HS, Griffin M, Houston JB. (2007). Evaluation of cryopreserved human hepatocytes as an alternative in vitro system to microsomes for the prediction of metabolic clearance. Drug Metab Dispos 35:293–301.
  • Davies B, Morris T. (1993). Physiological parameters in laboratory animals and humans. Pharm Res 10:1093–1095.
  • Gorski JC, Jones DR, Hamman MA, Wrighton SA, Hall SD. (1999). Biotransformation of alprazolam by members of the human cytochrome P4503A subfamily. Xenobiotica 29:931–944.
  • Grime K, Riley RJ. (2006). The impact of in vitro binding on in vitro-in vivo extrapolations, projections of metabolic clearance and clinical drug-drug interactions. Curr Drug Metab 7:251–264.
  • Hakooz N, Ito K, Rawden H, Gill H, Lemmers L, Boobis AR, Edwards RJ, Carlile DJ, Lake BG, Houston JB. (2006). Determination of a human hepatic microsomal scaling factor for predicting in vivo drug clearance. Pharm Res 23:533–539.
  • Hallifax D, Houston JB. (2006). Binding of drugs to hepatic microsomes: comment and assessment of current prediction methodology with recommendation for improvement. Drug Metab Dispos 34:724–6; author reply 727.
  • Hallifax D, Foster JA, Houston JB. (2010). Prediction of human metabolic clearance from in vitro systems: retrospective analysis and prospective view. Pharm Res 27:2150–2161.
  • Hallifax D, Houston JB. (2009). Methodological uncertainty in quantitative prediction of human hepatic clearance from in vitro experimental systems. Curr Drug Metab 10:307–321.
  • Hewitt NJ, Lechón MJ, Houston JB, Hallifax D, Brown HS, Maurel P, Kenna JG, Gustavsson L, Lohmann C, Skonberg C, Guillouzo A, Tuschl G, Li AP, LeCluyse E, Groothuis GM, Hengstler JG. (2007). Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev 39:159–234.
  • Ito K, Houston JB. (2004). Comparison of the use of liver models for predicting drug clearance using in vitro kinetic data from hepatic microsomes and isolated hepatocytes. Pharm Res 21:785–792.
  • Jones HM, Houston JB. (2004). Substrate depletion approach for determining in vitro metabolic clearance: time dependencies in hepatocyte and microsomal incubations. Drug Metab Dispos 32:973–982.
  • Kilford PJ, Gertz M, Houston JB, Galetin A. (2008). Hepatocellular binding of drugs: correction for unbound fraction in hepatocyte incubations using microsomal binding or drug lipophilicity data. Drug Metab Dispos 36:1194–1197.
  • Kilford PJ, Stringer R, Sohal B, Houston JB, Galetin A. (2009). Prediction of drug clearance by glucuronidation from in vitro data: use of combined cytochrome P450 and UDP-glucuronosyltransferase cofactors in alamethicin-activated human liver microsomes. Drug Metab Dispos 37:82–89.
  • Li AP. (2007). Human hepatocytes: isolation, cryopreservation and applications in drug development. Chem Biol Interact 168:16–29.
  • Lu C, Li P, Gallegos R, Uttamsingh V, Xia CQ, Miwa GT, Balani SK, Gan LS. (2006). Comparison of intrinsic clearance in liver microsomes and hepatocytes from rats and humans: evaluation of free fraction and uptake in hepatocytes. Drug Metab Dispos 34:1600–1605.
  • Obach RS. (1997). Nonspecific binding to microsomes: impact on scale-up of in vitro intrinsic clearance to hepatic clearance as assessed through examination of warfarin, imipramine, and propranolol. Drug Metab Dispos 25:1359–1369.
  • Obach RS. (1999). Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metab Dispos 27:1350–1359.
  • Obach RS, Reed-Hagen AE. (2002). Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos 30:831–837.
  • Rawden HC, Carlile DJ, Tindall A, Hallifax D, Galetin A, Ito K, Houston JB. (2005). Microsomal prediction of in vivo clearance and associated interindividual variability of six benzodiazepines in humans. Xenobiotica 35:603–625.
  • Sheiner LB, Beal SL. (1981). Some suggestions for measuring predictive performance. J Pharmacokinet Biopharm 9:503–512.
  • Soars MG, McGinnity DF, Grime K, Riley RJ. (2007). The pivotal role of hepatocytes in drug discovery. Chem Biol Interact 168:2–15.
  • Stringer R, Nicklin PL, Houston JB. (2008). Reliability of human cryopreserved hepatocytes and liver microsomes as in vitro systems to predict metabolic clearance. Xenobiotica 38:1313–1329.

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