424
Views
45
CrossRef citations to date
0
Altmetric
Review

Maximising use of in vitro ADMET tools to predict in vivo bioavailability and safety

, &
Pages 641-665 | Published online: 19 Oct 2007

Bibliography

  • DIMASI JA, HANSEN RW, GRABOWSKI HG: The price of innovation: new estimates of drug development costs. J. Health Econ. (2003) 22:151-185.
  • SERVICE RF: Surviving the Blockbuster syndrome. Science (2004) 303:1796-1799.
  • SCHMID EF, SMITH DA: R&D technology investments: misguided and expensive or a better way to discover medicines? Drug Discov. Today (2006) 11:775-784.
  • KOLA I, LANDIS J: Can the pharmaceutical industry reduce attrition rates? Nat. Rev. (2004) 3:711-715.
  • PENZOTTI JE, LANDRUM GA, PUTTA S: Building predictive ADMET models for early decisions in drug discovery. Curr. Opin. Drug Discov. Devel. (2004) 7:49-61.
  • WANG J, URBAN L: The impact of early ADME profiling on drug discovery and development strategy. Drug Discov. World (2004) 5:73-86.
  • KENNEDY T: Managing the drug discovery/development interface. Drug Discov. Tech. (1997) 2:436-441.
  • LI AP: Building predictive ADMET models for early decisions in drug discovery. Drug Discov. Today (2001) 6:357-366.
  • KERNS EH, DI L: Physicochemical profiling: overview of the screens. Drug Discov. Today Technol. (2004) 1(4):343-348.
  • THOMAS VH, BHATTACHAR S, HITCHINGHAM L et al.: The road map to oral bioavailability: an industrial perspective. Expert Opin. Drug Metab. Toxicol. (2006) 2(4):591-608.
  • BILLER SA, CUSTER L, DICKINSON KE et al.: The challenge of quality in candidate optimization. In: Pharmaceutical Profiling in Drug Discovery for Lead Selection. Borchardt RT, Kerns EH, Lipinski CA, Thakker DR, Wang B (Eds), AAPS Press (2004):413-429.
  • DI L, KERNS EH: Application of pharmaceutical profiling assays for optimization of drug-like properties. Curr. Opin. Drug Discov. Devel. (2005) 8(4):495-504.
  • FALLER B, WANG J, ZIMMERLIN A et al.: High-throughput in vitro profiling assays: lessons learnt from experiences at Novartis. Expert Opin. Drug Metab. Toxicol. (2006) 2(6):823-833.
  • LAHOZ1 A, GOMBAU1 L, DONATO MT, CASTELL JV, GÓMEZ-LECHÓN MJ: In vitro ADME medium/high-throughput screening in drug preclinical development. Mini Rev. Med. Chem. (2006) 6(9):1053-1062.
  • WANG J, FALLER B: Progress in bioanalytics and automation robotics for ADME screening. In: Comprehensive Medicinal Chemistry. ADME-Tox Approaches (2nd Edition), (Volume 5). Testa B, van de Waterbeemd H (Eds), Elsevier Ltd., Oxford, UK (2007):341-356.
  • EGAN WJ: Computational models for ADME. Ann. Rep. Med. Chem. (2007) 42:(In Press).
  • DI L, KERNS EH: Biological assay challenges from compound solubility: strategies for bioassay optimization. Drug Discov. Today (2006) 11:446-451.
  • DEWITTE RS: Avoiding physicochemical artefacts in early ADME–Tox experiments. Drug Discov. Today (2006) 11:855-859.
  • WUNBERG T, HENDRIX M, HILLISCH A et al.: Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits. Drug Discov. Today (2006) 11:175-180.
  • KERNS EH, DI L, BOURASSA J et al.: Integrity profiling of high throughput screening hits using LC-MS and related techniques. Comb. Chem. High Throuhput Screen. (2005) 8:459-466.
  • TAYLOR EW, QIANG MG, DOLLINGER GD: Simultaneous online characterization of small organic molecules derived from combinatorial libraries for identity, quantity, and purity by reversed-phase HPLC with chemiluminescent nitrogen, UV, and mass spectrometric detection. Anal. Chem. (1998) 70:3339-3347.
  • POPA-BURKE IG, ISSAKOVA O, ARROWAY JD et al.: Streamlined system for purifying and quantifying a diverse library of compounds and the effect of compound concentration measurements on the accurate interpretation of biological assay results. Anal. Chem. (2004) 76(24):7278-7287.
  • GUILORY JK, POUST RI: Chemical kinetics and drug stability. In: Drugs and the Pharmaceutical Sciences. Modern Pharmaceutics (3rd Edition), (Volume 72). Banker GS, Rhodes CT (Eds), Marcel Dekker, Inc., New York, USA (1996):179-211.
  • CARSTENSEN JT, RHODES CT (Eds): Drug stability. In: Drugs and the Pharmaceutical Sciences. (3rd Edition), (Volume 107). Marcel Dekker, Inc., New York, USA (2000).
  • KERNS EH, DI L: Chemical stability. In: Comprehensive Medicinal Chemistry. ADME-Tox Approaches (2nd Edition), (Volume 5). Testa B, van de Waterbeemd H (Eds), Elsevier Ltd., Oxford, UK (2007):489-507.
  • MEHTA AC: Analytical issues in the chemical stability testing of drugs in solution. Anal. Proc. (1995) 32(2):67-70.
  • HITCHINGHAM L, THOMAS VH: Development of a semi-automated chemical stability system to analyze solution based formulations in support of discovery candidate selection. J. Pharm. Biomed. Anal. (2007) 43(2):522-526.
  • LIPINSKI CA, LOMBARDO L, DOMINY BW, FEENEY PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. (1997) 23:3-25.
  • KIBBEY CE, POOLE SK, ROBINSON B, JACKSON JD, DURHAM D: An integrated process for measuring the physicochemical properties of drug candidates in a preclinical discovery environment. J. Pharm. Sci. (2001) 90:1164-1175.
  • BEVAN CD, LLOYD RS: A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates. Anal. Chem. (2000) 72:1781-1787.
  • KARIV I, ROURICK RA, KASSEL DB, CHUNG TDY: Improvement of “hit-to-lead” optimization by integration of in vitro HTS experimental models for early determination of pharmacokinetic properties. Comb. Chem. High Throughput Screen. (2002) 5:459-472.
  • STRESSER DM, BROUDY MI, HO T et al.: Highly selective inhibition of human CYP3A in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab. Dispos. (2004) 32:105-112.
  • PAN L, HO Q, TSUTSUI K, TAKAHASHI L: Comparison of chromatographic and spectroscopic methods used to rank compounds for aqueous solubility. J. Pharm. Sci. (2001) 90:521-529.
  • ZHOU L, YANG L, TILTON S, WANG J: Development of high throughput equilibrium solubility assay using miniaturized Shake-Flask method in early drug discovery. J. Pharm. Sci. (2007) 98:(In Press).
  • MCGOVERN SL, HELFAND BT, FENG B, SHOICHET BK: A specific mechanism of nonspecific inhibition. J. Med. Chem. (2003) 46:4265-4272.
  • SHOICHET BK: Screening in a spirit haunted world. Drug Discov. Today (2006) 11:607-615.
  • FENG BY, SHELAT A, DOMAN TN, GUY RK, SHOICHET BK: High-throughput assays for promiscuous inhibitors. Nat. Chem. Biol. (2005) 1(3):146-148.
  • FENG BY, SHOICHET BK: A detergent-based assay for the detection of promiscuous inhibitors. Nat. Protocols (2006) 1(2):550-553.
  • SEIDLER J, MCGOVERN SL, DOMAN TN, SHOICHET BK: Identification and prediction of promiscuous aggregating inhibitors among known drugs. J. Med. Chem. (2003) 46:4477-4486.
  • DE JOANNON AC, MANGANO G, PERI G, ROSSI V, MILANESE C: A flow-cytometric method to evaluate drug antiaggregating effect on rat neutrophils. J. Pharmacol. Toxicol. Metab. (1996) 36:21-28.
  • LEPOURCELET M, CHEN Y-NP, FRANCE DS et al.: Small-molecule antagonists of the oncogenic Tcf/β-catenin protein complex. Cancer Cells (2004) 5:91-102.
  • DALVIT C, CARONNI D, MONGELLI N, VERONESI M, VULPETTI A: NMR-based quality control approach for the identification of false positives and false negatives in high throughput screening. Curr. Drug Discov. Technol. (2006) 3(2):115-124.
  • AVDEEF A: In: Absorption and Drug Development, Solubility, Permeability and Charge State. Wiley-Interscience, Hoboken, New Jersey, USA (2003).
  • WAN H, ULANDER J: High-throughput pKa screening and prediction amenable for ADME profiling. Expert Opin. Drug Metab. Toxicol. (2006) 2(1):139-155.
  • CLEVELAND JA Jr, BENKO MH, GLUCK SJ, WALBROEHL YM: Automated pKa determination at low solute concentrations by capillary electrophoresis. J. Chromatogr. A (1993) 652:301-308.
  • ISHIHAMA Y, NAKAMURA M, MIWA T, KAJIMA T, ASAKAWA N: A rapid method for pKa determination of drugs using pressure-assisted capillary electrophoresis with photodiode array detection in drug discovery. J. Pharm. Sci. (2002) 91:933-942.
  • BOX K, BEVAN C, COMER J, HILL A, ALLEN R, REYNOLDS D: High-throughput measurement of pKa values in a mixed-buffer linear pH gradient system. Anal. Chem. (2003) 75:883-892.
  • LOMBARDO F, SHALAEVA M, TUPPER KA, GAO F, ABRAHAM MJ: ElogPoct: a tool for lipophilicity determination in drug discovery. J. Med. Chem. (2000) 43:2922-2928.
  • WOHNSLAND F, FALLER B: High-throughput permeability pH profile and high-throughput alkane/water LogP with artificial membranes. J. Med. Chem. (2001) 44:923-930.
  • AMIDON GL, LENNERNAS H, SHAH VP, CRISON JR: A theoretical basis for a biopharmaceutics drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. (1995) 12:413-420.
  • JAMES KC: Solubility and related properties. In: Drugs and the Pharmaceutical Sciences. (Volume 28). Marcel Dekker, Inc., New York, USA (1986):36-52.
  • YALKOWSKY SH, BANERJEE S: Aqueous Solubility Methods of Estimation for Organic Compounds. Marcel Dekker Inc., New York, USA (1992):149-154.
  • GRANT DJW, BRITTAIN HG: Solubility of pharmaceutical solids. In: Drugs and the Pharmaceutical Sciences, Physical Characterization of Pharmaceutical Solids. (Volume 70). Brittain HB (Ed.), Marcel Dekker, Inc., New York, USA (1995):321-386.
  • AVDEEF A, VOLOBOY D, FOREMAN A: Dissolution and solubility. In: Comprehensive Medicinal Chemistry, ADME-Tox Approaches. (2nd Edition), (Volume 5). Testa B, van de Waterbeemd H (Eds), Elsevier Ltd., Oxford, UK (2007):399-423.
  • BALAKIN KV: DMSO solubility and bioscreening. Curr. Drug Discov. (2003):27-30.
  • KERNS EH: High throughput physicochemical profiling for drug discovery. J. Pharm. Sci. (2001) 90:1838-1858.
  • GLOMME A, MARZ J, DRESSMAN JB: Comparison of a miniaturized Shake-Flask solubility method with automated potentiometric acid/base titrations and calculated solubilities. J. Pharm. Sci. (2005) 94(1):1-16.
  • CHEN XQ, VENKATESH S: Miniature device for aqueous and non-aqueous solubility measurements during drug discovery. Pharm. Res. (2004) 21(10):1758-1761.
  • BERGSTRÖM CAS, NORINDER U, LUTHMAN K, ARTURSSON P: Experimental and computational screening models for prediction of aqueous drug solubility. Pharm. Res. (2002) 19(2):182-188.
  • BERGSTRÖM CAS, LUTHMAN K, ARTURSSON P: Accuracy of calculated pH-dependent aqueous drug solubility. Eur. J. Pharm. Sci. (2004) 22(5):387-398.
  • TAN H, SEMIN D, WACKER M, CHEETHAM J: An automated screening assay for determination of aqueous equilibrium solubility enabling SPR study during drug lead optimization. JALA (2005) 10(6):364-373.
  • GALIA E, NICOLAIDES E, HORTER D, LOÈ BENBERG R, REPPAS C, DRESSMAN JB: Evaluation of various dissolution media for predicting in vivo performance of class I and II drugs. Pharm. Res. (1998) 15:698-705.
  • NICOLAIDES E, GALIA E, EFTHYMIOPOULOS C, DRESSMAN JB, REPPAS C: Forecasting the in vivo performance of four low solubility drugs from their in vitro dissolution data. Pharm. Res. (1999) 16:1876-1882.
  • DRESSMAN JB, REPPAS C: In vitro–in vivo correlations for lipophilic, poorly water-soluble drugs Eur. J. Pharm. Sci. (2000) 11(Suppl. 2):S73-S80.
  • KOSTEWICZ ES, BRAUNS U, BECKER R, DRESSMAN JB: Forecasting the oral absorption behavior of poorly soluble weak bases using solubility and dissolution studies in biorelevant media. Pharm. Res. (2002) 19:345-349.
  • KOSTEWICZ ES, WUNDERLICH M, BRAUNS U, BECKER R, BOCK T, DRESSMAN JB: Predicting the precipitation of poorly soluble weak bases upon entry in the small intestine. J. Pharm. Pharmacol. (2004) 56(1):43-51.
  • VERTZONI M, PASTELLI E, PSACHOULIAS D, KALANTZI L, REPPAS C: Estimation of intragastric solubility of drugs. Pharm. Res. (2007) 24(5):909-917.
  • LEVIS KA, LANE ME, CORRIGAN OI: Effect of buffer media composition on the solubility and effective permeability coefficient of ibuprofen. Int. J. Pharm. (2003) 253(1-2):49-59.
  • VERTZONI M, FOTAKI N, KOSTEWICZ E et al.: Dissolution media simulating the intralumenal composition of the small intestine: physiological issues and practical aspects. J. Pharm. Pharmacol. (2004) 56(4):453-462.
  • KALANTZI L, PERSSON E, POLENTARUTTI B et al.: Canine intestinal contents vs. simulated media for the assessment of solubility of two weak bases in the human small intestinal contents. Pharm. Res. (2006) 23(6):1373-1381.
  • OBATA K, SUGANO K, MACHIDA M, ASO Y: Biopharmaceutics classification by high throughput solubility assay and PAMPA. Drug Devel. Ind. Pharm. (2004) 30(2):181-185.
  • WEI H, LOEBENBERG R: Biorelevant dissolution media as a predictive tool for glyburide a class II drug. Eur. J. Pharm. Sci. (2006) 29(1):45-52.
  • PERSSON EM, GUSTAFSSON A-S, CARLSSON AS et al.: The effects of food on the dissolution of poorly soluble drugs in human and in model small intestinal fluids. Pharm. Res. (2005) 22(12):2141-2151.
  • AVDEEF A, BERGER CM, BROWNELL C: pH-Metric solubility. 2. Correlation between the acid-base titration and the saturation shake-flask solubility pH methods. Pharm. Res. (2000) 17(1):85-89.
  • STUART M, BOX K: Chasing equilibrium: measuring the intrinsic solubility of weak acids and bases. Anal. Chem. (2005) 77(4):983-990.
  • ARTURSSON P, NEUHOFF S, MATSSON P: Passive permeability and active transport models for prediction of oral absorption. In: Comprehensive Medicinal Chemistry. ADME-Tox Approaches (2nd Edition), (Volume 5). Testa B, van de Waterbeemd H (Eds), Elsevier Ltd., Oxford, UK (2007):259-278.
  • HAMALAINEN MD, FROSTELL-KARLSSON A: Predicting the intestinal absorption potential of hits and leads. Drug Discov. Today Technol. (2004) 1:397-406.
  • BALIMANE PV, HAN YH, CHONG S: Current industrial practices of assessing permeability and P-glycoprotein interaction. AAPS J. (2006) 8(1):E1-E13.
  • KANSY M, SENNER F, GUBERNATOR K: Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes. J. Med. Chem. (1998) 41:1007-1010.
  • AVDEEF A, STRAFFORD M, BLOCK E, BALOGH MP, CHAMBLISS W, KHAN I: Drug absorption in vitro model: filter-immobilized artificial membranes. 2. Studies of the permeability properties of lactones in piper methysticum forst. Eur. J. Pharm. Sci. (2001) 14:271-280.
  • SUGANO K, HAMADA H, MACHIDA M, USHIO H, SAITOH K, TERADA K: Optimized conditions of bio-mimetic artificial membrane permeability assay. Int. J. Pharm. (2001) 228:181-188.
  • RUELL JA, TSINMAN O, AVDEEF A: PAMPA – a drug absorption in vitro model. 12. Cosolvent method for permeability assays of amiodarone, itraconazole, tamoxifen, terfenadine, and other very insoluble molecules. Chem. Pharm. Bull. (2004) 52:561-565.
  • LIU H, SABUS C, CARTER GT, DU C, AVDEEF A, TISCHLER M: In vitro permeability of poorly aqueous soluble compounds using different solubilizers in the PAMPA assay with liquid chromatography/mass spectrometry detection. Pharm. Res. (2003) 20(11):1820-1826.
  • BENDELS S, TSINMAN O, WAGNER B et al.: PAMPA – excipient classification gradient map. Pharm. Res. (2006) 23(11):2525-2535.
  • KANSY M, FISCHER H, KRATZAT K, SENNER F, WAGNER B, PARRILLA I: High-throughput artificial membrane permeability studies in early lead discovery and development. In: Pharmacokinetic Optimization in Drug Research. Testa B, van de Waterbeemd H, Folkers G, Guy R (Eds), Verlag Helvetica Chimica Acta, Weinheim, Germany, New York, USA (2001):447-464.
  • BALIMANE PV, PACE E, CHONG S, ZHU M, JEMAL M, VAN PELT CK: A novel high-throughput automated chip-based nanoelectrospray tandem mass spectrometric method for PAMPA sample analysis. J. Pharm. Biomed. Anal. (2005) 39(1-2):8-16.
  • MENSCH J, NOPPE M, ADRIAENSEN J et al.: Novel generic UPLC/MS/MS method for high throughput analysis applied to permeability assessment in early drug discovery. J. Chromatogr. B Anal. Tech. Biomed. Life Sci. (2007) 847(2):182-187.
  • UNGELL AL, KARLSSON J: Cell culture in drug discovery: an industrial perspective. In: Drug Bioavailability. van de Waterbeemd H, Lennernas H, Artursson P (Eds), Wiley-VCH, Germany (2003):90-131.
  • ENGLUND G, RORSMAN F, ROENNBLOM A et al.: Regional levels of drug transporters along the human intestinal tract: co-expression of ABC and SLC transporters and comparison with Caco-2 cells. Eur. J. Pharm. Sci. (2006) 29(3-4):269-277.
  • ARTURSSON P, TAVELIN S: Caco-2 and emerging alternatives for prediction of intestinal drug transport: a general overview. In: Drug Bioavailability. van de Waterbeemd H, Lennernas H, Artursson P (Eds), Wiley-VCH, Germany (2003):72-89.
  • LENNERNAS H, LUNDGREN E: Intestinal and blood–brain drug transport: beyond involvement of a single transport function. Drug Discov. Today Technol. (2004) 1:417-422.
  • UNGELL A-LB: Caco-2 replace or refine? Drug Discov. Today Technol. (2004) 1:423-430.
  • STEFFANSEN B, NIELSEN CU, BRODIN B, ERIKSSON AH, ANDERSEN R, FROKJAER S: Intestinal solute carriers: an overview of trends and strategies for improving oral drug absorption. Eur. J. Pharm. Sci. (2004) 21(1):3-16.
  • LIANG E, CHESSIC K, YAZDANIAN M: Evaluation of an accelerated Caco-2 cell permeability model. J. Pharm. Sci. (2000) 89(3):336-345.
  • ALSENZ J, HAENEL E: Development of a 7-Day, 96-Well Caco-2 Permeability assay with high-throughput direct UV compound analysis. Pharm. Res. (2003) 20(12):1961-1969.
  • LAKERAM M, LOCKLEY DJ, SANDERS DJ, PENDLINGTON R, FORBES B: Paraben transport and metabolism in the biomimetic artificial membrane permeability assay (BAMPA) and 3-day and 21-day Caco-2 cell systems. J. Biomol. Screen. (2007) 12(1):84-91.
  • YAMASHITA S, KONISHI K, YAMAZAKI Y et al.: New and better protocols for a short-term Caco-2 cell culture system. J. Pharm. Sci. (2002) 91(3):669-679.
  • MIRET S, ABRAHAMSE L, DE GROENE EM: Comparison of in vitro models for the prediction of compound absorption across the human intestinal mucosa. J. Biomol. Screen. (2004) 9(7):598-606.
  • SAUNDERS KC: Automation and robotics in ADME screening. Drug Discov. Today Technol. (2004) 1:373-380.
  • KERNS EH, DI L, PETUSKY S, FARRIS M, LEY R, JUPP P: Combined application of parallel artificial membrane permeability assay and Caco-2 permeability assays in drug discovery. J. Pharm. Sci. (2004) 93(6):1440-1453.
  • MARINO AM, YARDE M, PATEL H, CHONG S, BALIMANE PV: Validation of the 96 well Caco-2 cell culture model for high throughput permeability assessment of discovery compounds. Int. J. Pharm. (2005) 297(1-2):235-241.
  • BALIMANE PV, PATEL K, MARINO A, CHONG S: Utility of 96 well Caco-2 cell system for increasing throughput of P-gp screening in drug discovery. Eur. J. Pharm. Biopharm. (2004) 58:99-105.
  • YAMASHITA S, FURUBAYASHI T, KATAOKA M, SAKANE T, SEZAKI H, TOKUDA H: Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells. Eur. J. Pharm. Sci. (2000) 10(3):195-204.
  • SAHA P, KOU JH: Effect of bovine serum albumin on drug permeability estimation across Caco-2 monolayers. Eur. J. Pharm. Biopharm. (2002) 54(3):319-324.
  • NEUHOFF S, ARTURSSON P, ZAMORA I, UNGELL A-L: Impact of extracellular protein binding on passive and active drug transport across Caco-2 cells. Pharm. Res. (2006) 23(2):350-359.
  • HOCHMAN JH, YAMAZAKI M, OHE T, LIN JH: Evaluation of drug interactions with P-glycoprotein in drug discovery: in vitro assessment of the potential for drug-drug interactions with P-glycoprotein. Curr. Drug Metab. (2002) 3(3):257-273.
  • VARMA MVS, PERUMAL OP, PANCHAGNULA R: Functional role of P-glycoprotein in limiting peroral drug absorption: optimizing drug delivery. Curr. Opin. Chem. Biol. (2006) 10(4):367-373.
  • TROUTMAN MD, Thakker DR: Efflux ratio cannot assess P-glycoprotein-mediated attenuation of absorptive transport: asymmetric effect of P-glycoprotein on absorptive and secretory transport across caco-2 cell monolayers. Pharm. Res. (2003) 20:1200-1209.
  • NOBILI S, LANDINI I, GIGLIONI B, MINI E: Pharmacological strategies for overcoming multidrug resistance. Curr. Drug Targets (2006) 7(7):861-879.
  • KUPPENS IELM, BREEDVELD P, BEIJNEN JH, SCHELLENS JHM: Modulation of oral drug bioavailability: from preclinical mechanism to therapeutic application. Cancer Invest. (2005) 23(5):443-464.
  • TROUTMAN MD, THAKKER DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm. Res. (2003) 20:1210-1224.
  • BALIMANE PV, CHONG S, MORRISON RA: Current methodologies used for evaluation of intestinal permeability and absorption. J. Pharmacol. Toxicol. (2000) 44:301-312.
  • IRVINE JD, TAKAHASHI L, LOCKHART K et al.: MDCK (Madin-Darby canine kidney) cells: a tool for membrane permeability screening. J. Pharm. Sci. (1999) 88:28-33.
  • BOHETS H, ANNAERT P, MANNENS G et al.: Strategies for absorption screening in drug discovery and development. Curr. Top. Med. Chem. (2001) 1:367-383.
  • VARMA MVS, ASHOKRAJ Y, CHINMOY SD, PANCHAGNULA R: P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacol. Res. (2003) 48(4):347-359.
  • BOURDET DL, THAKKER DR: Saturable absorptive transport of the hydrophilic organic cation ranitidine in Caco-2 cells: role of pH-dependent organic cation uptake system and P-glycoprotein. Pharm. Res. (2006) 23(6):1165-1177.
  • VARMA MVS, SATEESH K, PANCHAGNULA R: Functional role of P-glycoprotein in limiting intestinal absorption of drugs: contribution of passive permeability to P-glycoprotein mediated efflux transport. Mol. Pharm. (2005) 2(1):12-21.
  • ARELLANO C, PHILIBERT C, VACHOUX C, WOODLEY J, HOUIN G: The metabolism of midazolam and comparison with other CYP enzyme substrates during intestinal absorption: in vitro studies with rat everted gut sacs. J. Pharm. Pharmaceut. Sci. (2007) 10(1):26-36.
  • COTREAU MM, VON MOLTKE LL, BEINFELD MC, GREENBLATT DJ: Methodologies to study the induction of rat hepatic and intestinal cytochrome P450 3A at the mRNA, protein, and catalytic activity level. J. Pharm. Toxicol. Methods (2000) 43:41-54.
  • DRESCHER S, GLAESER H, MURDTER T, HITZL M, EICHELBAUM M, FROMM MF: P-glycoprotein-mediated intestinal and biliary digoxin transport in humans. Clin. Pharmacol. Ther. (2003) 73:223-231.
  • WATKINS PB, WRIGHTON SA, SCHUETZ EG, MOLOWA DT, GUZELIAN PS: Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J. Clin. Invest. (1987) 80:1029-1036.
  • KIVISTO KT, NIEMI M, FROMM MF: Functional interaction of intestinal CYP3A4 and P-glycoprotein. Fund. Clin. Pharmacol. (2004) 18:621-626.
  • LIN JH, YAMAZAKI M: Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin. Pharmacokinet. (2003) 42:59-98.
  • LIN JH, CHIBA M, CHEN IW et al.: Effect of dexamethasone on the intestinal first-pass metabolism of indinavir in rats: evidence of cytochrome P-450 3A and P-glycoprotein induction. Drug Metab. Dispos. (1999) 27:1187-1193.
  • CUMMINS CL, SALPHATI L, REID MJ, BENET LZ: In vivo modulation of intestinal CYP3A metabolism by P-glycoprotein: studies using the rat single-pass intestinal perfusion model. J. Pharmacol. Exp. Ther. (2003) 305:306-314.
  • LI LY, AMIDON GL, KIM JS et al.: Intestinal metabolism promotes regional differences in apical uptake of indinavir: coupled effect of P-glycoprotein and cytochrome P450 3A on indinavir membrane permeability in rat. J. Pharmacol. Exp. Ther. (2002) 301:586-593.
  • MOHRI K, UESAWA Y: Enzymatic activities in the microsomes prepared from rat small intestinal epithelial cells by differential procedures. Pharm. Res. (2001) 18:1232-1236.
  • CUMMINS CL, JACOBSEN W, BENET LZ: Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J. Pharmacol. Exp. Ther. (2002) 300:1036-1045.
  • HOCHMAN JH, CHIBA M, NISHIME J, YAMAZAKI M, LIN JH: Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4. J. Pharmacol. Exp. Ther. (2000) 292:310-318.
  • BRIMER C, DALTON JT, ZHU Z et al.: Creation of polarized cells coexpressing CYP3A4, NADPH cytochrome P450 reductase and MDR1/P-glycoprotein. Pharm. Res. (2000) 17:803-810.
  • LIN JH, CHIBA M, BAILLIE TA: Is the role of the small intestine in first-pass metabolism overemphasized? Pharmacol. Rev. (1999) 51:135-158.
  • CHAUBAL MV: Application of drug delivery technologies in lead candidate selection and optimization. Drug Discov. Today (2004) 9(14):603-609.
  • NEERVANNAN S: Preclinical formulations for discovery and toxicology: physicochemical challenges. Expert Opin. Drug Metab. Toxicol. (2006) 2(5):715-731.
  • POUTON CW: Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur. J. Pharm. Sci. (2006) 29(3-4):278-287.
  • MOUNTFIELD RJ, SENEPIN S, SCHLEIMER M, WALTER I, BITTNER B: Potential inhibitory effects of formulation ingredients on intestinal cytochrome P450. Int. J. Pharm. (2000) 211(1-2):89-92.
  • WAGNER D, SPAHN-LANGGUTH H, HANAFY A, KOGGEL A, LANGGUTH P: Intestinal drug efflux: formulation and food effects. Adv. Drug Deliv. Rev. (2001) 50(Suppl. 1):S13-S31.
  • MERISKO-LIVERSIDGE E, LIVERSIDGE GG, COOPER ER: Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur. J. Pharm. Sci. (2003) 18(2):113-120.
  • DUBEY R: Impact of nanosuspension technology on drug discovery & development. Drug Deliv. Technol. (2006) 6(5):67-71.
  • KOCBEK P, BAUMGARTNER S, KRISTL J: Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. Int. J. Pharm. (2006) 312(1-2):179-186.
  • CHEN H, ZHANG Z, MCNULTY C et al.: A high-throughput combinatorial approach for the discovery of a cremophor EL-free paclitaxel formulation. Pharm. Res. (2003) 20:1302-1308.
  • GARDNER CR, ALMARSSON O, CHEN H et al.: Application of high throughput technologies to drug substance and drug product development. Comp. Chem. Eng. (2004) 28(6-7):943-953.
  • OBACH RS: The prediction of human clearance from hepatic microsomal metabolism data. Curr. Opin. Drug Discov. Dev. (2001) 4:36-44.
  • NARITOMI Y, TERASHITA S, KIMURA S, SUZUKI A, KAGAYAMA A, SUGIYAMA Y: Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans. Drug Metab. Dispos. (2001) 29:1316-1324.
  • OBACH RS, BAXTER JG, LISTON TE et al.: The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J. Pharmacol. Exp. Ther. (1997) 283:46-58.
  • OBACH RS: 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. (1999) 27:1350-1359.
  • LAU YY, KRISHNA G, YUMIBE NP et al.: The use of in vitro metabolic stability for rapid selection of compounds in early discovery based on their expected hepatic extraction ratios. Pharm. Res. (2002) 19:1606-1610.
  • WIENKERS LC, HEATH TG: Predicting in vivo drug interactions from in vitro drug discovery data. Nat. Rev. Drug Discov. (2005) 4:825-833.
  • LIN JH, WONG BK: Complexities of glucuronidation affecting in vitro in vivo extrapolation. Curr. Drug Metab. (2002) 3:623-646.
  • LINGET JM, DU VIGNAUD P: Automation of metabolic stability studies in microsomes, cytosol and plasma using a 215 Gilson liquid handler. J. Pharm. Biomed. Anal. (1999) 19:893-901.
  • CALDWELL GW, MASUCCI JA, CHACON E: High throughput liquid chromatography-mass spectrometry assessment of the metabolic activity of commercially available hepatocytes from 96-well plates. Comb. Chem. High Throughput Screen. (1999) 2:39-51.
  • KORFMACHER WA, PALMER CA, NARDO C et al.: Development of an automated mass spectrometry system for the quantitative analysis of liver microsomal incubation samples: a tool for rapid screening of new compounds for metabolic stability. Rapid Commun. Mass Spectr. (1999) 13:901-907.
  • DI L, KERNS EH, GAO N et al.: Experimental design on single-time-point high-throughput microsomal stability assay. J. Pharm. Sci. (2004) 93(6):1537-1544.
  • DI L, KERNS EH, LI SQ, PETUSKY SL: High throughput microsomal stability assay for insoluble compounds. Int. J. Pharm. (2006) 317:54-60.
  • MCGINNITY DF, SOARS MG, URBANOWICZ RA, RILEY RJ: Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance. Drug Metab. Dispos. (2004) 32:1247-1253.
  • REDDY A, HEIMBACH T, FREIWALD S et al.: Validation of a semi-automated human hepatocyte assay for the determination and prediction of intrinsic clearance in discovery. J. Pharm. Biomed. Anal. (2005) 37:319.
  • PATSALOS PN, PERUCCA E: Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs. Lancet Neurol. (2003) 2(6):347-356.
  • OBACH RS, WALSKY RL, VENKATAKRISHNAN K, GAMAN EA, HOUSTON JB, TREMAINE LM: The utility of in vitro cytochrome P450 inhibition data in the prediction of drug–drug interactions. J. Pharmacol. Exp. Ther. (2006) 316(1):336-348.
  • BJORNSSON TD, CALLAGHAN JT, EINOLF HJ et al.: The conduct of in vitro and in vivo drug–drug interaction studies: a pharmaceutical research and manufacturers of America (PhRMA) perspective. Drug Metab. Dispos. (2003) 31:815-832.
  • CRESPI CL, MILLER VP, PENMAN BW: Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450. Anal. Biochem. (1997) 248:188-190.
  • RILEY RJ, GRIME K: Metabolic screening in vitro: metabolic stability, CYP inhibition and induction. Drug Discov. Today Technol. (2004) 1:365-372.
  • COHEN LH, REMLEY MJ, RAUNIG D, VAZ ADN: In vitro drug interactions of cytochrome P450: an evaluation of fluorogenic to conventional substrates. Drug Metab. Dispos. (2003) 31:1005-1015.
  • BUSBY WF Jr, ACKERMANN JM, CRESPI CL: Effect of methanol, ethanol, dimethyl sulfoxide, and acetonitrile on in vitro activities of CDNA-expressed human cytochromes P-450. Drug metabol. Dispos. (1999) 27:246-249.
  • ITO K, HALLIFAX DR, OBACH S, HOUSTON BJ: Impact of parallel pathways of drug elimination and multiple cytochrome P450 involvement on drug-drug interactions: CYP2D6 paradigm. Drug Metabol. Dispos. (2005) 33:837-844.
  • HICKMAN D, WANG J-P, WANG Y, UNADKAT JD: 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. (1998) 26(3):207-215.
  • KIM M-J, KIM H, CHA I-J et al.: High-throughput screening of inhibitory potential of nine cytochrome P450 enzymes in vitro using liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectr. (2005) 19(18):2651-2658.
  • LIN JH: CYP induction-mediated drug interactions: in vitro assessment and clinical implications. Pharm. Res. (2006) 23(6):1089-1116.
  • WAHLSTROM JL, ROCK DA, SLATTER JG, WIENKERS LC: Advances in predicting CYP-mediated drug interactions in the drug discovery setting. Expert Opin. Drug Discov. (2006) 1(7):677-691.
  • PELKONEN O, MANENPAA J, TAAVITSAINEN P, RAUTIO A, RAUTIO H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotics (1998) 28:1203-1253.
  • SHIMADA T, YAMAZAKI H, MIMURA M, INUI Y, GUENGERICH FP: Interindividual variations in human liver cytochromes P450 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. (1994) 270:414-423.
  • LECLUYSE EL: Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur. J. Pharm. Sci. (2001) 13:343-368.
  • CUI X, THOMAS A, HAN Y et al.: Quantitative PCR assay for cytochromes P450 2B and 3A induction in rat precision-cut liver slices: correlation study with induction in vivo. J. Pharmacol. Toxicol. Methods (2005) 52(2):234-243.
  • HEALAN-GREENBERG C, WARING JF: Application of new screening methods to assess induction of hepatic drug metabolizing enzymes. Am. Pharm. Rev. (2006) 9(3):115-118.
  • MILLS JB, ROSE KA, SADAGOPAN N, SAHI J, DE MORAIS SM: Induction of drug metabolism enzymes and MDR1 using a novel human hepatocyte cell line. J. Pharmacol. Exp. Ther. (2004) 309:303-309.
  • WILLSON TM, KLIEWER SA: PXR, CAR and drug metabolism. Nat. Rev. Drug Discov. (2002) 1:259-266.
  • HANDSCHIN C, MEYER UA: Induction of drug metabolism: the role of nuclear receptors. Pharmacol. Rev. (2003) 55:649-673.
  • EL-SANKARY W, GIBSON GG, AYRTON A, PLANT N: Use of a reporter gene assay to predict and rank the potency and efficacy of CYP3A4 inducers. Drug Metab. Dispos. (2001) 29:1499-1504.
  • LUO G, CUNNINGHAM M, KIM S et al.: CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab. Dispos. (2002) 30:795-804.
  • SANGUINETTI MC, TRISTANI-FIROUZI M: hERG potassium channels and cardiac arrhythmia. Nature (2006) 440:463-469.
  • REDFERN WS, CARLSSONB L, DAVISC AS et al.: Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc. Res. (2003) 58(1):32-45.
  • GOLDKIND L, LAINE L: A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience. Pharmacoepidemiol. Drug Saf. (2006) 15(4):213-220.
  • LASSER KE, ALLAN PD, WOOLHANDLER SJ, HIMMELSTEIN DU, WOLFE SM, BOR DH: Timing of new blackbox warnings and withdrawals for prescription medications. JAMA (2002) 287:2215-2220.
  • WHITEBREAD S, HAMON J, BOJANIC D, URBAN L: In vitro safety pharmacology profiling: an essential tool for drug development. Drug Discov. Today (2005) 10:1421-1433.
  • KEATING MT, SANGUINETTI MC: Molecular and cellular mechanisms review of cardiac arrhythmias. Cell (2001) 104:569-580.
  • RODEN DM, JEFFREY R, BALSER JR, GEORGE AL Jr, ANDERSON ME: Cardiac ion channels. Annu. Rev. Physiol. (2002) 64:431-475.
  • CHIU PJS, MARCOE KF, BOUNDS SE et al.: Validation of a [3H]astemizole binding assay in hek293 cells expressing HERG K+ channels. J. Pharmacol. Sci. (2004) 95:311-319.
  • DIAZ JG, DANIELL K, LEITZA ST et al.: The [3H]dofetilide binding assay is a predictive screening tool for hERG blockade and proarrhythmia: comparison of intact cell and membrane preparations and effects of altering [K+]. J. Pharmacol. Toxicol. Methods (2004) 50:187-199.
  • PEARLSTEIN R, VAZ R, RAMPE D: Understanding the structure-activity relationship of the human ether-a-go-go-related gene cardiac K+ Channel. A model for bad behavior. J. Med. Chem. (2003) 46:1-6.
  • WIBLE BA, HAWRYLUK P, ECKHARD FE, KURYSHEV YK, KIRSCH G, BROWN AM: HERG-lite: a novel comprehensive high-throughput screen for drug-induced hERG risk. J. Pharmacol. Toxicol. Methods (2005) 52:136-145.
  • KIRSCH GE, TREPAKOVA ES, BRIMECOMBE JC et al.: Variability in the measurement of hERG potassium channel inhibition: effects of temperature and stimulus pattern. J. Pharmacol. Toxicol. Methods (2004) 50(2):93-101.
  • FUNG M, THORNTON A, MYBECK K, HSIAO-HUI W, HORNBUCKLE K, MUNIZ E: Evaluation of the characteristics of safety withdrawal of prescription drugs from worldwide pharmaceutical markets-1960 – 1999. Drug Infect. J. (2001) 35:293-317.
  • KAPLOWITZ N: Idiosyncratic drug hepatotoxicity. Nat. Rev. Drug. Discov. (2005) 4:489-499.
  • TEMPLE RJ, HIMMEL MH: Safety of newly approved drugs: implications for prescribing. JAMA (2002) 287(17):2273-2275.
  • HOFFMAN DJ, SEIFERT T, BORRE A, NELLANS HN: Method to estimate the rate and extent of intestinal absorption in conscious rats using an absorption probe and portal blood sampling. Pharm. Res. (1995) 12:889-894.
  • MCCLAVE SA, SNIDER HL: Dissecting the energy needs of the body. Curr. Opin. Clin. Nutr. Metab. Care (2001) 4:143-147.
  • O'BRIEN PJ, CHAN K, SILBER PM: Human and animal hepatocytes in vitro with extrapolation in vivo. Chem. Biol. Interact. (2004) 150:97-114.
  • O'BRIEN PJ, IRWIN W, DIAZ D et al.: High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high contentscreening. Arch. Toxicol. (2006) 80:580-604.
  • XU JJ, DIAZ D, O'BRIEN PJ: Applications of cytotoxicity assays and prelethal mechanistic assays for assessment of human hepatotoxicity potential. Chem. Biol. Interact. (2004) 150:115-128.
  • OLSON H, BETTON G, ROBINSON D et al.: Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul. Toxicol. Pharmacol. (2000) 32:56-67.
  • DAMBACH DM, ANDREWS BA, MOULIN F: New technologies and screening strategies for hepatotoxicity: use of in vitro models. Toxicol. Pathol. (2005) 33:17-26.
  • FARKAS D, TANNENBAUM SR: In vitro methods to study chemically-induced hepatotoxicity: a literature review. Curr. Drug Metab. (2005) 6:111-125.
  • MORELLI JK, BUEHRLE M, POGNAN F, BARONELR, FIELES W, CIACCIO PJ: Validation of an in vitro screen for phospholipidosis using a high-content biology platform. Cell Biol. Toxicol. (2006) 22:15-27.
  • SAKURAI A, KURATA A, ONISHI Y, HIRANO H, ISHIKAWA T: Prediction of drug-induced intrahepatic cholestasis: in vitro screening and QSAR analysis of drugs inhibiting the human bile salt export pump. Expert Opin. Drug Saf. (2007) 6:71-86.
  • ALLEN JW, KHETANI SR, BHATIA SN: In vitro zonation and toxicity in a hepatocyte bioreactor. Toxicol. Sci. (2005) 84:110-119.
  • LIU TV, CHEN AA, CHO LM et al.: Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels. FASEB J. (2007) 21:790-801.
  • GRIBALDO L: Haematotoxicology: scientific basis and regulatory aspects. Altern. Lab. Anim. (2002) 2:111-113.
  • PESSINA A, MALERBA I, GRIBALDO L: Hematotoxicity testing by cell clonogenic assay in drug development and preclinical trials. Curr. Pharm. Des. (2005) 11:1055-1065.
  • RICH IN, HALL KM: Validation and development of a predictive paradigm for hemotoxicology using a multifunctional bioluminescence colony-forming proliferation assay. Toxicol. Sci. (2005) 87(2):427-441.
  • RICH IN: High-throughput in vitro hemotoxicity testing and in vitro cross-platform comparative toxicity. Expert Opin. Drug Metab. Toxicol. (2007) 3:295-307.
  • HARRY GJ, TIFFANY-CASTIGLIONI E: Evaluation of neurotoxic potential by use of in vitro systems. Expert Opin. Drug Metab. Toxicol. (2005) 1:701-713.
  • BRAT DJ, BRIMIJOIN S: A paradigm for examining toxicant effects on viability, structure, and axonal transport of neurons in culture. Mol. Neurobiol. (1992) 6(2-3):125-135.
  • KIRKLAND D, AARDEMA M, HENDERSON L, MULLER L: Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. sensitivity, specificity and relative predicitivity. Mutat. Res. (2005) 584:1-256.
  • SUTER W: Predictive value of in vitro safety studies. Curr. Opin. Chem. Biol. (2006) 10:362-366.
  • LANG C, MEIER Y, STIEGER B et al.: Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury. Pharmacogenet. Genomics (2007) 17:47-60.
  • HASTWELL PW, CHAI L-L, ROBERTS KJ et al.: High-specificity and high-sensitivity genotoxicity assessment in a human cell line: validation of the GreenScreen HC GADD45a-GFP genotoxicity assay. Mutat. Res. (2006) 607:160-175.
  • KREJSA CM, HORVATH D, ROGALSKI SL et al.: Predicting ADME properties and side effects: the BioPrint approach. Curr. Opin. Drug Discov. Devel. (2003) 6:470-480.
  • BENDER A, JENKINS JL, GLICK M et al.: Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effect from chemical structure. Chem. Med. Chem. (2007) 2:1-14.
  • BALANI SK, MIWA GT, GAN L-S, WU J-T, LEE FW: Strategy of utilizing in vitro and in vivo ADME tools for lead optimization and drug candidate selection. Curr. Top. Med. Chem. (2005) 5(11):1033-1038.
  • STONER CL, GIFFORD E, STANKOVIC C et al.: Implementation of an ADME enabling selection and visualization tool for drug discovery. J. Pharm. Sci. (2004) 93(5):1131-1141.
  • BLEICHER KH, BOEHM H-J, MUELLER K, ALANINE AI: A guide to drug discovery: hit and lead generation: beyond high-throughput screening. Nat. Rev. Drug Discov. (2003) 2(5):369-378.
  • GRIBBON P, SEWING A: High-throughput drug discovery: what can we expect from HTS? Drug Discov. Today (2005) 10(1):17-22.
  • RECANATINI M, POLUZZI E, MASETTI M, CAVALLI A, DE PONTI F: QT prolongation through hERG K+ channel blockade: current knowledge and strategies for the early prediction during drug development. Med. Res. Rev. (2005) 25(2):133-166.
  • FARID R, DAY T, FRIESNER RA, PEARLSTEIN RA: New insights about HERG blockade obtained from protein modeling, potential energy mapping, and docking studies. Bioorg. Med. Chem. (2006) 14(9):3160-3173.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.