Advances in in vitro drug metabolism screening

Abstract Developments in automation, analytical technologies and molecular biology are being exploited by drug metabolism scientists in order to provide enhanced in vitro systems for the study of the metabolic disposition of potential drug candidates. Routine investigation of factors such as metabolic stability and induction and inhibition of drug metabolizing enzymes is now preferred in the early stages of drug discovery. This, in turn, should provide a greater understanding of the underlying principles governing these processes and allow a greater role for drug metabolism in the design of new drug molecules.

[1]  R. Fisher,et al.  Comparative analysis of cytochrome P4503A induction in primary cultures of rat, rabbit, and human hepatocytes. , 1995, Drug metabolism and disposition: the biological fate of chemicals.

[2]  J V Castell,et al.  A microassay for measuring cytochrome P450IA1 and P450IIB1 activities in intact human and rat hepatocytes cultured on 96-well plates. , 1993, Analytical biochemistry.

[3]  M. T. Donato,et al.  Effect of model inducers on cytochrome P450 activities of human hepatocytes in primary culture. , 1995, Drug metabolism and disposition: the biological fate of chemicals.

[4]  D J Rance,et al.  The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. , 1997, The Journal of pharmacology and experimental therapeutics.

[5]  R Temple,et al.  Understanding consequences of concurrent therapies. , 1993, JAMA.

[6]  A. D. Rodrigues,et al.  Use of in vitro human metabolism studies in drug development. An industrial perspective. , 1994, Biochemical pharmacology.

[7]  P. Corey,et al.  Incidence of Adverse Drug Reactions in Hospitalized Patients , 2012 .

[8]  T. Sueyoshi,et al.  The Nuclear Orphan Receptor CAR-Retinoid X Receptor Heterodimer Activates the Phenobarbital-Responsive Enhancer Module of the CYP2B Gene , 1998, Molecular and Cellular Biology.

[9]  D. Moore,et al.  A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements , 1994, Molecular and cellular biology.

[10]  B. Ring,et al.  In vitro methods for assessing human hepatic drug metabolism: their use in drug development. , 1993, Drug metabolism reviews.

[11]  R. Williams,et al.  Bioartificial liver support: developments in hepatocyte culture and bioreactor design. , 1997, British medical bulletin.

[12]  A. Nomeir,et al.  Validation of a rapid microtiter plate assay to conduct cytochrome P450 2D6 enzyme inhibition studies , 1998 .

[13]  Y. Sugiyama,et al.  Quantitative prediction of in vivo drug clearance and drug interactions from in vitro data on metabolism, together with binding and transport. , 1998, Annual review of pharmacology and toxicology.

[14]  J. S. Sidhu,et al.  Modulation of xenobiotic-inducible cytochrome P450 gene expression by dexamethasone in primary rat hepatocytes. , 1995, Pharmacogenetics.

[15]  J. Lehmann,et al.  The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. , 1998, The Journal of clinical investigation.

[16]  A. Parkinson.  An Overview of Current Cytochrome P450 Technology for Assessing the Safety and Efficacy of New Materials , 1996, Toxicologic pathology.

[17]  J B Houston,et al.  Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. , 1997, Drug metabolism reviews.

[18]  Rodrigues Ad,et al.  Preclinical drug metabolism in the age of high-throughput screening: an industrial perspective. , 1997 .

[19]  C. Goodfellow,et al.  Improving the in vivo duration of 5-lipoxygenase inhibitors: application of an in vitro glucuronosyltransferase assay. , 1997, Drug metabolism and disposition: the biological fate of chemicals.

[20]  A. Po,et al.  What lessons can be learnt from withdrawal of mibefradil from the market? , 1998, The Lancet.

[21]  B. W. Penman,et al.  Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450. , 1997, Analytical biochemistry.

[22]  D. Moore,et al.  Differential Transactivation by Two Isoforms of the Orphan Nuclear Hormone Receptor CAR* , 1997, The Journal of Biological Chemistry.

[23]  A. Li,et al.  Optimization of cryopreservation procedures for rat and human hepatocytes. , 1989, Xenobiotica; the fate of foreign compounds in biological systems.

[24]  A. Anderson,et al.  Localization of a phenobarbital-responsive element (PBRE) in the 5'-flanking region of the rat CYP2B2 gene. , 1995, Gene.

[25]  Y. Fujii‐Kuriyama,et al.  Distinct effects of phenobarbital and its N-methylated derivative on liver cytochrome P450 induction. , 1996, Archives of biochemistry and biophysics.

[26]  P. Maurel,et al.  Long-term primary cultures of adult human hepatocytes. , 1997, Chemico-biological interactions.

[27]  R. Plumb,et al.  Application of a generic fast gradient liquid chromatography tandem mass spectrometry method for the analysis of cytochrome P450 probe substrates. , 1998, Rapid communications in mass spectrometry : RCM.

[28]  B. Rohde,et al.  Prediction of In Vivo Drug Interaction from In Vitro Systems Exemplified by Interaction Between Verapamil and Cimetidine Using Human Liver Microsomes and Primary Hepatocytes , 1997, Journal of clinical pharmacology.

[29]  J Kvĕtina,et al.  Presence and activity of cytochrome P450 isoforms in minipig liver microsomes. Comparison with human liver samples. , 1998, Drug metabolism and disposition: the biological fate of chemicals.

[30]  B. Weatherley,et al.  Sodium valproate acutely inhibits lamotrigine metabolism. , 1992, British journal of clinical pharmacology.

[31]  V. Dixit.  Development of a bioartificial liver using isolated hepatocytes. , 1994, Artificial organs.

[32]  S. Binkley,et al.  Comparisons of phase I and phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey. , 1995, Drug metabolism and disposition: the biological fate of chemicals.

[33]  J. Bolton,et al.  Metabolic screening using on-line ultrafiltration mass spectrometry. , 1998, Drug metabolism and disposition: the biological fate of chemicals.

[34]  B. Kennedy,et al.  Refinement of an in vitro cell model for cytochrome P450 induction. , 1998, Drug metabolism and disposition: the biological fate of chemicals.

[35]  J. Cashman.  Drug discovery and drug metabolism , 1996 .

[36]  L. Azároff,et al.  Phenobarbital induction of cytochrome P-450 gene expression. , 1992, The Biochemical journal.

[37]  J. Lehmann,et al.  An Orphan Nuclear Receptor Activated by Pregnanes Defines a Novel Steroid Signaling Pathway , 1998, Cell.