ADME References

Drug Metabolism—General [TOP]
Eddershaw PJ, Beresford AP and Bayliss MK (2000) ADME/PK as part of a rational approach to drug discovery. Drug Discovery Today, 5:409-414.

Smith DA (2000) Induction and drug development. Eur J Pharm Sci. 11:185-189.

White RE (2000) High-throughput screening in drug metabolism and pharmacokinetic support of drug discovery. Annu Rev Pharmacol Toxicol. 40:133-157.

Levy RH, Thummel KE, Trager WF, Hansten PD and Eichelbaum M Eds. (2000) Metabolic Drug Interactions. Lippincott Williams & Wilkins.

Obach, SR (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 Dispo. 27(11):1350-1359.

Smith DA and van de Waterbeemd H (1999) Pharmacokinetics and metabolism in early drug discovery. Curr Op Chem Biol. 3:373-378.

Ito K, Iwatsubo T, Kanamitsu S, Nakajima Y and Sugiyama Y (1998) Annu Rev Pharmacol Toxicol. Quantitative prediction of in vivo drug clearance and drug interactions from in vitro data on metabolism, together with binding and transport. 38:461-499. 1998

Lin JH and Lu AY (1998) Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet. 35:361-390.

Houston JB and Carlile DJ (1997) Prediction of hepatic clearance from microsomes, hepatocytes and liver slices. Drug Metab Rev. 29:891-922.

Lin JH and Lu AY (1997) Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol Rev. 49:403-49.

Gibson, GG and Skett P (1994) Introduction to Drug Metabolism. Blackie Academic & Professional.

Drug Metabolism and Disposition (Vol. 26, No. 12 – entire issue).

Cytochrome P450 [TOP]
REVIEWS
Phillips IR and Shepard EA (ed. 1998) Cytochrome P450 Protocols. Methods in Molecular Biology. Vol. 107, Humana Press.

Rendic S and DiCarlo FJ (1997) Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev. 29:413-580.

C Ioannides (ed. 1996) Cytochromes P450 — Metabolic and Toxicological Aspects. CRC Press.

Nelson RD, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC and Nebert DW (1996) P450 superfamily:update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics, 6:1-42.

Ortiz de Montellano PR (ed. 1995) Cytochrome P450 — Structure, Mechanism, and Biochemistry. Plenum Press.

Waterman MR and Johnson EF. Eds. (1991) Methods in Enzymology. Cytochrome P450. Vol. 206. Academic Press.

JOURNAL ARTICLES

Wang RW, Newton DJ, Liu N, Atkins WM and Lu AY (2000) Human cytochrome P450 3A4: in vitro drug-drug interaction patterns are substrate-dependent. Drug Metab Dispos.28:360-366.

Crespi CL and Miller VP (1999) The use of heterologusly expressed drug metabolizing enzymes — state of the art and prospects for the future. Pharmacol Ther. 84:121-131.

Shiraga T, Kaneko H, Iwasaki K, Tozuka Z, Suzuki A, and T Hata (1999) Identification of cytochrome P450 enzymes involved in the metabolism of zotepine, an antipsychotic drug, in human liver microsomes. Xenobiotica, 29(3): 217-229.

Kenworthy KE, Bloomer JC, Clarke SE and Houston JB (1999) CYP3A4 drug interactions: correlation of 10 in vitro probe substrates. Br J Clin Pharmacol. 48:716-727.

De Wildt SN, Kearns GL, Leeder JS, and van den Anker JN (1999) Cytochrome P450 3A:ontogeny and drug disposition. Clin Pharmacokinet. 37:485-505.

Lin JH and Lu AY (1998) Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet. 35(5): 361-390.

Thummel KE and Wilkinson GR (1998) in vitro and in vivo drug interactions involving human CYP3A. Annu Rev Toxicol. 38:389-430.

Clarke SE (1998) in vitro assessment of human cytochrome P450. Xenobiotica, 28(12):1167-1202.

Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ and Wastall PJ (1997) The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. Pharmacol Exp Ther. 283(1):46-58.

Yamazaki H, Inoue K, Turvy CG, Guengerich FP, Shimada T (1997) Effects of freezing, thawing, and storage of human liver samples on the microsomal contents and activities of cytochrome P450 enzymes. Drug Metab Dispos. 25(2):168-74.

Pearce RE, McIntyre CJ, Madan A, Sanzgiri U, Draper AJ, Bullock PL, Cook DC, Burton LA, Latham J, Nevins C and Parkinson A (1996) Effects of freezing, thawing, and storing human liver microsomes on cytochrome P450 activity. Arch Biochem Biophys. 331(2):145-69.

Shimada T, Yamazaki H, Mimura M, Inui Y and Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423

Forrester LM, Henderson CJ, Glancey MJ, Back DJ, Park BK, Ball SE, Kitteringham NR, McLaren AW, Miles JS, Skett P, Wolf CR (1992) Relative expression of cytochrome P450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics. Biochem. J. 281( Pt 2):359-68

The following papers review the RAF and RSF approach to designing experiments and interpreting data using cDNA-expressed enzymes.

Roy P, Yu LJ, Crespi CL and Waxman DJ (1999) Development of a substrate-activity based approach to identify the major human liver P450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P450 profiles. Drug Metab Dispos. 27(6):655-666.

Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H and Yokoi T (1999) Azelastine N-demethylation by cytochrome P-450 CYP3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of an approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 27:1381-1391.

Crespi CL and Penman BW (1997) Use of cDNA-expressed human cytochrome P450 enzymes to study potential drug-drug interactions. Adv Pharmacol. 43:171-188.

Fluorometric Cytochrome P450 Assays [TOP]
Stresser DM (2004) High-throughput screening of human cytochrome P450 inhibitors using fluorometric substrates: Methodology for 25 enzyme substrate pairs. In "Optimization in Drug Discovery: In Vitro Methods" (Z. Yan and G. W. Caldwell eds) in series "Methods in Pharmacology and Toxicology (YJ Kang, series ed), Humana press, Totowa, NJ, USA

Ekins S, Stresser DM and Williams JA (2003) In vitro and pharmacophore insights for CYP3A enzymes. Trends Pharm. Sci. 24: 161-166

Kragie L, Turner SD, Patten CJ, Crespi CL and Stresser DM (2002) Assessing pregnancy risks of azole antifungals using a high throughput aromatase inhibition assay. Endocrine Research, 28: 129-140.

Crespi CL, Miller VP and Stresser DM (2002) Design and application of fluorometric assays for human cytochrome P450 inhibition. Methods in Enzymology 357:276-284.

Yamamoto, T, Suzuki, A and Kohno, Y. (2002) Application of Microtiter Palte Assay to Evaluate Inhibitory Effects of Various Compounds on Nine Cytochrome P450 Isoforms and to Estimate their Inhibition Patterns. Drug metabol. Pharmacokin. 17(5):437-448.

Chauret N, Dobbs B, Lackman RL, Bateman K, Nicoll-Griffith DA, Stresser DM, Ackermann JA, Turner SD, Miller VP and Crespi CL (2001) The use of 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC) as a specific CYP2D6 probe in human liver microsomes. Drug Metab Dispos.29:1196-1200.

Crespi CL, and Stresser DM (2000) Fluorometric screening for metabolism-based drug-drug interactions. J Pharmacol Toxicol Methods, 44(1):325-31.

Stresser DM, Blanchard AP, Turner SD, Erve JCL, Dandeneau AA, Miller VP and Crespi CL (2000) Substrate-dependent modulation of CYP3A4 catalytic activity: analysis of 27 test compounds with four fluorometric substrates. Drug Metab Dispos. 28: 1440-1448.

Price RJ, Surry D, Renwick AB, Meneses-Lorente G, Lake BG and Evans DC (2000) CYP isoform induction screening in 96-well plates: use of 7-benzyloxy-4-trifluoromethylcoumarin as a substrate for studies with rat hepatocytes. Xenobiotica, 30:781-795.

Stresser DM, Turner SD, McNamara J, Stocker P, Miller VP, Crespi CL and Patten CJ (2000) A high-throughput screen to identify inhibitors of aromatase (CYP19). Anal. Biochem. 284:427-430.

Crespi CL (1999) Higher-throughput screening with human cytochromes P450. Current Opinion in Drug Discovery & Development, 2(1):15-19.

Favreau LV, Palamanda JR, Lin CC, and Nomeir AA (1999) Improved reliability of the rapid microtiter plate assay using recombinant enzyme in predicting CYP2D6 inhibition in human liver microsomes. Drug Metab Dispos. 27:436-439.

Onderwater RC, Venhorst J, Commandeur JN and Vermeulen NP (1999) Design, synthesis, and characterization of 7-methoxy-4-(aminomethyl)coumarin as a novel and selective cytochrome P450 2D6 substrate suitable for high-throughput screening. Chem Res Toxicol. 7:555-559.

Chauret N, Tremblay N, Lackman RL, Gauthier JY, Silva JM, Marois J, Yergey JA, and Nicoll-Griffith DA (1999) Description of a 96-well plate assay to measure cytochrome P4503A inhibition in human liver microsomes using a selective fluorescent probe. Anal Biochem. 276(2):215-26.

Henderson GL, Harkey MR, Gershwin ME, Hackman RM, Stern JS and Stresser DM (1999) Effects of ginseng components on cDNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci. 65(15):209-214.

Crespi CL, Miller VP and Penman BW (1998) High throughput screening for inhibition of cytochrome P450 metabolism. Med Chem Res. 8(7/8): 457-471.

Crespi CL, Miller VP and Penman BW (1997) Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450. Anal. Biochem. 248(1):188-90.

Organic Solvent Effects [TOP]
Busby Jr. WF, Ackermann JR, and Crespi CL. (1999) Effect of methanol, ethanol, dimethyl sulfoxide, and acetonitrile on in vitro activities of cDNA-expressed human cytochromes P-450. Drug Metab. Dispos. 27(2):246-249.

Chauret N, Gauthier A and Nicoll-Griffith DA (1998) Effect of common organic solvents on in vitro cytochrome P450-mediated metabolic activities in human liver microsomes. Drug Metab Dispos. 1:1-4.

Hickman D, Wang JP, Wang Y and Unadkat JD (1998) Evaluation of the selectivity of in vitro probes and suitability of organic solvents for the measurement of human cytochrome P450 monooxygenase activities. Drug Metab Dispos. 3:207-15.

Protein Binding Effects [TOP]
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. 11:1350-9.

Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ, and Wastall PJ (1997) The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. 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. Pharmacol Exp Ther. 283(1):46-58.

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. 12:1359-69.

UGT [TOP]
Tukey RH and Strassburg CP (2000) Human UDP-Glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol. 40:581-616.

Burchell B, Brierley CH and Rance D (1995) Specificty of human UDP-glucuronosyltransferases and xenobiotic glucuronidation. Life Sci. 57:1819-1831.

Burchell B, McGurk K, Brierley B and Clarke DJ (1997) UDP-glucuronosyltransferases. In “Comprehensive Toxicology, vol 3:Biotransformation”. (F.P. Guengerich, ed) Pergamon Elsevier, New York.

FMO [TOP]
Cashman JR, Akerman BR, Forrest SM, and Treacy EP (2000) Population-specific polymorphisms of the human FMO3 gene: significance for detoxication. Drug Metab Dispos. 28:169-73.

Pike MG, Martin YN, Mays DC, Benson LM, Naylor S and Lipsky JJ. (1999) Roles of FMO and CYP450 in the metabolism in human liver microsomes of S-methyl-N,N-diethyldithiocarbamate, a disulfiram metabolite. Alcohol Clin Exp Res. 7:1173-9.

Grothusen A, Hardt J, Brautigam L, Lang D and Bocker R (1996) A convenient method to discriminate between cytochrome P450 enzymes and flavin-containing monooxygenases in human liver microsomes. Arch Toxicol. 71:64-71.

Cashman JR (1995) Structural and catalytic properties of the mammalian flavin-containing monooxygenase. Chem Res. Toxicol. 8:166-181.

Cashman JR, Park SB, Berkman CE, and Cashman LE (1995) Role of hepatic flavin-containing monooxygenase 3 in drug and chemical metabolism in adult humans. Chem Biol Interact. 96:33-46.

Poulsen LL and Ziegler DM (1995) Multisubstrate flavin-containing monooxygenases: applications of mechanism to specificity. Chem Biol Interact. 96:57-73.

Hines RN, Cashman JR, Philpot RM, Williams DE and Ziegler DM (1994) The mammalian flavin-containing monooxygenases: molecular characterization and regulation of expression. Toxicol Appl Pharmacol. 125:1-6.

Lawton MP, Cashman JR, Cresteil T, Dolphin CT, Elfarra AA, Hines RN, Hodgson E, Kimura T, Ozols J, Phillips IR, Philpot RM, Poulsen LL, Rettie AE, Shepard EA, Williams DE, and Ziegler DM (1994) A nomenclature for the mammalian flavin-containing monooxygenase gene family based on amino acid sequence identities. Arch. Biochem. Biophys. 308(1):254-257.

P-Glycoprotein (MDR1) [TOP]
Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I and Gottesman MM (1999) Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol & Toxicol. 39: 361-398.

Sharom FJ, Yu X, Lu P, Liu R, Chu JWK, Szabo K, Muller M, Hose CD, Monks A, Varadi A, Seprodi J, and Sarkadi B (1999) Interaction of the P-glycoprotein multidrug transporter (MDR1) with high affinity peptide chemosensitizers in isolated membranes, reconstituted systems, and intact cells. Biochemical Pharmacology, 58: 571-586.

Bellamy WT (1996) P-glycoproteins and multidrug resistance. Annu Rev Pharmacol. Toxicol. 36:161-83.

Gottesman, M.M. and Pastan, I (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem. 62:385-427.

P-Glycoprotein ATPase Assay [TOP]
Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I and Gottesman MM (1999) Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol & Toxicol. 39: 361-397.

Drueckes P, Schinzel R, and Palm D (1995) Photometric microtiter assay of inorganic phosphate in the presence of acid-labile organic phosphates. Anal. Biochem 230:173-77.

Scarborough GA (1995) Drug-stimulated ATPase activity of the human P-glycoprotein. J. Bioenergetics and Biomembranes, 27, No. 1: 37-41.

Sarkadi B, Price EM, Boucher RC, Germann UA and Scarborough GA (1992) Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase. J Biol Chem. 267, No. 7: 4854-4858.

Boulton DW, DeVane CL, Histon HL and Markowitz JS In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci. 71(2):163-9, 2002

P-Glycoprotein Uptake and Ligand-Binding Assays [TOP]
Sharom FJ, Yu X, Lu P, Liu R, Chu, JWK, Szabo K, Muller M, Hose CD, Monks A, Varadi A, Seprodi J and Sarkadi B (1999) Interaction of the P-glycoprotein multidrug transporter (MDR1) with high affinity peptide chemosensitizers in isolated membranes, reconstituted systems, and intact cells. Biochemical Pharmacology, 58: 571-586.

Hepatocytes [TOP]
Price RJ, Surry D, Renwick AB, Meneses-Lorente G, Lake BG and Evans DC (2000) CYP isoform induction screening in 96-well plates: use of 7-benzyloxy-4-trifluoromethylcoumarin as a substrate for studies with rat hepatocytes. Xenobiotica, 30:781-795.

LeCluyse E, Madan A, Hamilton G, Carroll K, DeHaan R, and Parkinson A (2000) Expression and regulation of cytochrome P450 enzymes in primary cultures of human hepatocytes. J Biochem Mol Toxicol. 14(4):177-88.

Guyomard C, Rialland L, Fremond B, Chesne C and Guillouzo A (1996) Influence of Alginate Gel Entrapment and Cryopreservation on Survival and Xenobiotic Metabolism Capacity of Rat Hepatocytes. Toxicol. Appl. Pharmacol. 141:349-356.

Fremond B, Malandain C, Guyomard C, Chesne C, Guillouzo A and Campion JP (1993) Correction of bilirubin conjugation in the gunn rat using hepatocytes immobilized in alginate gel beads as an extracorporeal bioartificial liver. Cell Transplant, 2:453-460.

Species Differences [TOP]
Chauret N, Gauthier A, Martin J, Nicoll-Griffith DA (1997) in vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat, and horse. Drug Metab Dispos 25:1130-1136.

Sharer JE, Shipley LA, Vandenbranden MR, Binkley SN, Wrighton SA (1995) Comparisons of phase I and phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey. Drug Metab Dispos, 23:1231-1241.

MAO References: [TOP]

• Kalgutkar, A.S., Dalvie, D.K., Castagnoli, N., and Taylor, T.J. (2001) Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isozymes A and B: SAR studies on MAO substrates and inhibitors, Chemical Research in Toxicology, 14, 1139-1162.
• Benedetti, M.S. (2001) Biotransformation of xenobiotics by amine oxidases, Fundamentals of Clinical Pharmacology, 15, 75-84.
• Youdim, M.B.H and Finberg, J.P.M (1991) New directions in monoamine oxidase A and B selective inhibitors and substrates, Biochemical Pharmacology, 41, 155-162.

NAT References: [TOP]

1. Rogers, L.E., Levy, G.N. and Weber, W.W. (1998) Substrate selectivity of mouse N-acetyltransferases 1, 2, and 3 expressed in COS-1 cells, Drug Metabolism and Disposition, 26, 502-505.
2. Grant, D.M., Goodfellow, G.H., Sugamori, K. and Durette, K. (2000) Pharmacogenetics of human arylamine N-acetyltransferases, Pharmacology, 61, 204-211.
3. Ilett, K.F., Kadlubar, F.F. and Minchin, R.F. (1999) 1998 International meeting of the arylamine N-acetyltransferases: Synopsis of the workshops on nomenclature, biochemistry, molecular biology, interspecies comparisons, and role in human disease risk, Drug Metabolism and Disposition, 27, 957-959.
4. deBethizy, J.D. and Hayes, J.R. (2001) Metabolism: A determinant of toxicity. In: Principles and Methods of Toxicology, ed. Hayes, A.W., p.77-136.