Chapter 7: Biokinetics

van de Waterbeemd H. , Smith D.A. , & Jones B.C. (2001). Lipophilicity in PK design: methyl, ethyl, futile. Journal of Computer-Aided Molecular Design 15, 273–286.

Abraham M.H. , Martins F. , & Mitchell R.C. (1997). Algorithms for skin permeability using hydrogen bond descriptors: the problem of steroids. Journal of Pharmacy and Pharmacology 49, 858–865.

Abraham M.H. , Chadha H.S. , Martins F. , Mitchell R.C. , Bradbury M.W. , & Gratton J.A. (1999). Hydrogen bonding part 46: a review of the correlation and prediction of transport properties by an LFER method: physicochemical properties, brain penetration and skin permeability. Pesticide Science 55, 78–88.

Cronin M.T.D. , Dearden J.C. , Worth A.P. , & Walker J.D. (2002). QSARs for predicting environmental-human health interactions. Environmental Toxicology and Chemistry, in press.

Cronin M.T.D. , Dearden J.C. , & Moss G.P. (2002). QSARs for the penetration of chemicals across human, fish and artificial membranes — mechanistic considerations. In Quantitative Structure–Activity Relationships in Environmental Sciences, Vol. VIII (ed. Walker J.D. ). Pensacola, FL, USA: SETAC Press, in press.

Archer G. , Balls M. , Bruner L.H. , Curren R.D. , Fentem J.H. , Holzhütter H-G. , Liebsch M. , Lovell D.P. , & Southee J.A. (1997). The validation of toxicological prediction models. ATLA 25, 505–516.

Worth A.P. , Barratt M.D. , & Houston J.B. (1998). The validation of computational prediction techniques. ATLA 26, 241–247.

Worth A.P. , & Balls M. (2001). The importance of the prediction model in the development and validation of alternative tests. ATLA 29, 135–143.

Moss G.P. , Dearden J.C. , Patel H. , & Cronin M.T.D. (2002). Quantitative structure–permeability relationships (QSPRs) for percutaneous absorption. Toxicology in Vitro, 299–317.

Cronin M.T.D. , Dearden J.C. , Moss G.P. , & Murray-Dickson G. (1999). Investigation of the mechanism of flux across human skin in vitro by quantitative structure-permeability relationships. European Journal of Pharmaceutical Sciences 7, 325–330.

Lipinski C.A. , Lombardo F. , Dominy B.W. , & Feeney P.J. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 23, 3–25.

Tice T.M. (2001). Selecting the right compounds for screening: does Lipinski's Rule of 5 for pharmaceuticals apply to agrochemicals? Pesticide Management Science 57, 3–16.

Howes D. , Guy R. , Hadgraft J. , Heylings J. , Hoeck U. , Kemper F. , Maibach H. , Marty J-P. , Merk H. , Parra J. , Rekkas D. , Rondelli I. , Schaefer H. , Täuber U. , & Verbiese N. (1996). Methods for assessing percutaneous absorption. The report and recommendations of ECVAM workshop 13. ATLA 24, 81–106.

OECD (2000). Draft Test Guideline No. 428: Skin Absorption — In Vitro Method, 8 pp. Paris, France: Organisation for Economic Cooperation and Development.

Diembeck W. , Beck H. , Benech-Kieffer F. , Courtellemont P. , Dupuis J. , Lovell W. , Paye M. , Spengler J. , & Steiling W. (1999). Test guidelines for in vitro assessment of dermal absorption and percutaneous penetration of cosmetic ingredients. Food and Chemical Toxicology 37, 191–205.

OECD (2000). Draft Test Guideline No. 427: Skin Absorption — In Vivo Method, 8 pp. Paris, France: Organisation for Economic Cooperation and Development.

Scott R.C. , Batten P.L. , Clowes H.M. , Jones B.K. , & Ramsey J.D. (1992). Further validation of an in vitro method to reduce the need for in vivo studies for measuring the absorption of chemicals through the skin. Fundamental and Applied Toxicology 19, 484–492.

ECETOC (1993). ECETOC Monograph No. 20: Percutaneous Absorption, 80 pp. Brussels, Belgium: European Centre for Ecotoxicology and Toxicology of Chemicals.

Bronaugh R.L. , & Stewart R.F. (1984). Methods for in vitro percutaneous absorption studies III. Hydro-phobic compounds, 20 pp. Journal of Pharmaceutical Sciences 73, 1255–1259.

OECD (2000). Draft Guidance Document for the Conduct of Skin Absorption Studies. Paris, France: Organisation for Economic Cooperation and Development.

Stanley S.D. , & Wilding I.R. (2001). Oral drug absorption studies: the test model for man is man. Drug Discovery Today 6, 127–128.

Ayrton A. , & Morgan P. (2001). Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica 31, 469–407.

Li A.P. (2001). Screening for human ADME/Tox drug proteins in drug discovery. Drug Discovery Today 6, 357–366.

Le Ferrec E. , Chesne C. , Artusson P. , Brayden D. , Fabre G. , Gires P. , Guillou F. , Rousset M. , Rubas W. , & Scarino M.L. (2001). In vitro models of the intestinal barrier. The report and recommendations of ECVAM workshop 46. ATLA 29, 649–668.

Hidalgo I.J. , Raub T.J. , & Borchardt R.T. (1989). Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96, 736–49.

Ungell A-L. (1997). In vitro absorption studies and their relevance to absorption from the GI tract. Drug Development and Industrial Pharmacy 23, 879–892.

Lennernas H. (1998). Human intestinal permeability. Journal of Pharmaceutical Sciences 87, 403–410.

Taipalensuu J. , Tornblom H. , Lindberg G. , Einarsson C. , Sjoquist F. , Melhus H. , Garberg P. , Sjostrom B. , Lundgren B. , & Artursson P. (2001). Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers. Journal of Pharmacology and Experimental Therapeutics 299, 164–170.

Stanness K.A. , Westrum L.E. , Fornaciari E. , Mascagni P. , Nelson J.A. , Stenglein S.G. , Myers T. , & Janigro D. (1997). Morphological and functional characterization of an in vitro blood–brain barrier model. Brain Research 771, 329–342.

Kusuhara H. , & Sugiyama Y. (2001). Efflux transport systems for drugs at the blood–brain barrier and blood–fluid–cerebrospinal fluid barrier (part 1). Drug Discovery Today 6, 150–156.

Cestelli A. , Catania C. , D'Agostino S. , Di Liegro I. , Licata L. , Schiera G. , Pitarresi G.L. , Savettieri G. , De Caro V. , Giandalia G. , & Giannola L.I. (2001). Functional feature of a novel model of blood–brain barrier: studies on permeation of test compounds. Journal of Controlled Release 76, 139–147.

Garberg P. (1998). In vitro models of the blood–brain barrier. ATLA 26, 821–847.

Veronesi B. , & Ehrich M. (1999). Cell culture models of environmental chemical neurotoxicity. In Neurotoxicology In Vitro (ed. Pentreath V.W. ), pp. 239–268. London, UK: Taylor & Francis.

Foster K.A. , & Roberts M.S. (2000). Experimental methods for studying drug uptake in the head and brain. Current Drug Metabolism 1, 333–356.

Clarke S.E. (1998). In vitro assessment of human cytochrome P450. Xenobiotica 28, 1167–1202.

Soucek P. (1999). Expression of cytochrome P450 2A6 in Escherichia coli: purification, spectral and catalytic characterization, and preparation of poly-clonal antibodies. Archives of Biochemistry and Biophysics 370, 190–200.

Masimirembwa C.M. , Otter C. , Berg M. , Jonsson M. , Leidvik B. , Jonsson E. , Johansson T. , Backman A. , Edlund A. , & Andersson T.B. (1999). Heterologous expression and kinetic characterization of human cytochromes P450: validation of a pharmaceutical tool for drug metabolism research. Drug Metabolism and Disposition 27, 1117–1122.

Ozawa S. , Ohta K. , Miyajima A. , Kurebayashi H. , Sunouchi M. , Shimizu M. , Murayama N. , Matsumoto Y. , Fukuoka M. , & Ohno Y. (2000). Metabolic activation of o-phenylphenol to a major cytotoxic metabolite, phenylhydroquinone: role of human CYP1A2 and rat CYP2C11/CYP2E1. Xenobiotica 30, 1005–1017.

Tanaka E. , Terada M. , & Misawa S. (2000). Cytochrome P4502E1: its clinical and toxicological role. Journal of Clinical Pharmacy and Therapeutics 25, 165–175.

Riley R.J. , Parker A.J. , Trigg S. , & Manners C.N. (2001). Development of a generalized, quantitative physicochemical model of CYP3A4 inhibition for use in early drug discovery. Pharmaceutical Research 18, 652–655.

Sheweita S.A. (2001). Drug-metabolizing enzymes: mechanisms and functions. Current Drug Metabolism 1, 107–132.

Burchell B. , Soars M. , Monaghan G. , Cassidy A. , Smith D. , & Ethell B. (2000). Drug-mediated toxicity caused by genetic deficiency of UDP-glucurono-syltransferases. Toxicology Letters 112-113, 333–340.

Glatt H. (2000). Sulfotransferases in the bioactivation of xenobiotics. Chemico-Biological Interactions 129, 141–70.

MacGregor J.T. , Collins J.M. , Sugiyama Y. , Tyson C.A. , Dean J. , Smith L. , Andersen M. , Curren R.D. , Houston J.B. , Kadlubar F.F. , Kedderis G.L. , Krishnan D. , Li A.P. , Parchment R.E. , Thummel K. , Tomaszewski J.E. , Ulrich R. , Vickers A.E.M. , & Wrighton S.A. (2001). In vitro human tissue models in risk assessment: report of a consensus-building workshop. Toxicological Sciences 59, 17–36.

OECD (1984). OECD Guidelines for the Testing of Chemicals No. 417: Toxicokinetics. Paris, France: Organisation for Economic Cooperation and Development.

Coecke S. , Rogiers V. , Bayliss M , Castell J. , Doehmer J. , Fabre G. , Fry J. , Kern A. , & Westmoreland C. (1999). The use of long-term hepatocyte cultures for detecting induction of drug metabolising enzymes: the current status. ECVAM hepatocytes and metabolically competent systems task force report 1. ATLA 27, 579–605.

Doehmer J. , Buters J.T. , Luch A. , Soballa V. , Baird W.M. , Morisson H. , Stegeman J.J. , Townsend A.J. , Greenlee W.F. , Glatt H.R. , Seidel A. , Jacob J. , & Greim H. (1999). Molecular studies on the toxifying effects by genetically engineered cytochromes P450. Drug Metabolism Reviews 31, 423–435.

Coecke S. , Catalani P. , Bull S. , Langezaal I. , Bogni A. , Bremer S. , & Balls M. (2000). The integrated use of a genetically engineered cell line panel harbouring drug metabolising enzymes to detect metabolism-related problem compounds. In Progress in the Reduction, Refinement, and Replacement of Animal Experimentation (ed. Balls M. , van Zeller A-M. , & Halder M.E. ), pp. 147–157. Amsterdam, The Netherlands: Elsevier.

Coecke S. , Bogni A. , Worth A. , Hartung T. , & Monshouwer M. (2001). The use of genetically engineered cells for assessing CYP2D6-related polymorphic effects. Toxicology in Vitro 15, 553–556.

Houston J.B. , & Carlile D.J. (1987). Prediction of hepatic clearance from microsomes, hepatocytes and liver slices. Drug Metabolism Reviews 29, 891–922.

Obach R.S. (2001). The prediction of human clearance from hepatic microsomal metabolism data. Current Opinion in Drug Discovery and Development 41, 36–44.

Ito K. , Iwatsubo T. , Kanamitsu S. , Nakajima Y. , & Sugiyama Y. (1998). Quantitative prediction of in vivo drug clearance and drug interactions from in vitro data on metabolism, together with binding and transport. Annual Review of Pharmacology and Toxicology 38, 461–499.

Dearden J.C. , Barratt M.D. , Benigni R. , Bristol D.W. , Combes R.D. , Cronin M.T.D. , Judson P.M. , Payne M.P. , Richard A.M. , Tichy M. , Worth A.P. , & Yourick J.J. (1997). The development and validation of expert systems for predicting toxicity. The report and recommendations of an ECVAM/ECB workshop (ECVAM workshop 24). ATLA 25, 223–252.

Cronin M.T.D. (2001). Computational methods for the prediction of drug toxicity. Current Opinion in Drug Discovery and Development 3, 292–297.

Greene N. , Judson P.N. , Langowski J.J. , & Marchant C.A. (1999). Knowledge-based expert systems for toxicity and metabolism predictions: DEREK, StAR and METEOR. SAR & QSAR in Environmental Research 10, 299–314.

Lewis D.F.V. , Ioannides C. , & Parke D.V. (1998). An improved and updated version of the compact procedure for the evaluation of P450-mediated chemical activation. Drug Metabolism Reviews 30, 709–737.

Parke D.V. , Ioannides C. , & Lewis D.F.V. (1990). The safety evaluation of drugs and chemicals by the use of computer optimised molecular parametric analysis of chemical toxicity (COMPACT). ATLA 18, 91–102.

Brown S.J. , Raja A.A. , & Lewis D.F.V. (1994). A comparison between COMPACT and Hazard Expert evaluations for 80 chemicals tested by the NTP/NCI rodent bioassay. ATLA 22, 482–500.

Lewis D.F.V. , Lake B.G. , George S.G. , Dickins M. , Eddershaw P.J. , Tarbit M.H. , Beresford A.P. , Goldfarb P.S. , & Guengerich F.P. (1999). Molecular modelling of CYP1 family enzymes CYP1A1, CYP1A2, CYP1A6, and CYP1B1 based on sequence homology with CYP1O2. Toxicology 139, 53–79.

Klopman G. , Diumayuga M. , & Galafgous J. (1994). META. 1. A program for the evaluation of metabolic transformation of chemicals. Journal of Chemical Information and Computer Sciences 34, 1320–1325.

Talafous J. , Sayre L.M. , Mieyal J.J. , & Klopman G. (1994). META. 2. A dictionary model of mammalian xenobiotic metabolism. Journal of Chemical Information and Computer Sciences 34, 1326–1333.

Bull S. , Langezaal I. , Clothier R. , & Coecke S. (2001). A genetically engineered cell-based model system for detecting metabolism-mediated toxicity. ATLA 29, 703–716.

Ma Y. , Lang L. , Kiesewetter D.O. , Jagoda E. , Sassaman M.B. , Der M. , & Eckelman W.C. (2001). Liquid chromatography–tandem mass spectrometry identification of metabolites of two 5-HT1A antagonists, N-[2-[4-(2-methoxylphenyl)piperazino]ethyl]-N-(2-pyridyl) trans- and cis-4-fluorocyclohexane-carboxamide, produced by human and rat hepatocytes. Journal of Chromatography B — Biomedical Applications 755, 47–56.

Kassahun K. , Pearson P.G. , Tang W. , McIntosh I. , Leung K. , Elmore C. , Dean D. , Wang R. , Doss G. , & Baillie T.A. (2001). Studies on the metabolism of troglitazone to reactive intermediates in vitro and in vivo: evidence for novel biotransformation pathways involving quinone methide formation and thiazolidinedione ring scission. Chemical Research in Toxicology 4, 62–70.

Schmalix W.A. , Lang D. , Schneider A. , Bocker R. , Greim H. , & Doehmer J. (1996). Stable expression and coexpression of human cytochrome P450 oxi-doreductase and cytochrome P4501A2 in V79 Chinese hamster cells: sensitivity to quinones and biotransformation of 7-alkoxyresorufins and tri-azines. Drug Metabolism and Disposition 24, 1314–1319.

Philip P.A. , Ali-Sadat S. , Doehmer J. , Kocarek T. , Akhtar A. , Lu H. , & Chan K.K. (1999). Use of V79 cells with stably transfected cytochrome P450 cDNAs in studying the metabolism and effects of cytotoxic drugs. Cancer Chemotherapy and Pharmacology 43, 59–67.

Linget J.M. , & du Vignaud P. (1999). Automation of metabolic stability studies in microsomes, cytosol and plasma using a 215 Gilson liquid handler. Journal of Pharmaceutical and Biomedical Analysis 19, 893–901.

Swales N.J. , & Utesch D. (1998). Metabolic activity of fresh and cryopreserved dog hepatocyte suspensions. Xenobiotica 28, 937–948.

Miller V.P. (2000). Fluorometric high-throughput screening for inhibitors of cytochrome P450. Annals of the New York Academy of Sciences 919, 26–32.

Li A.P. , Lu C. , Brent J.A. , Pham C. , Fackett A. , Ruegg C.E. , & Silber P.M. (1999). Cryopreserved human hepatocytes: characterization of drug-metabolizing enzyme activities and applications in higher throughput screening assays for hepatotoxi-city, metabolic stability, and drug–drug interaction potential. Chemico-Biological Interactions 121, 17–35.

Rodrigues A.D. (1999). Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomes. Biochemical Pharmacology 57, 465–480.

Gómez-Lechón M.J. , Donato T. , Jover R. , Rodriguez C. , Ponsoda X. , Glaise D. , Castell J.V. , & Guguen-Guillouzo C. (2001). Expression and induction of a large set of drug-metabolising enzymes by the highly differentiated human hepatoma cell line BC2. European Journal of Biochemistry 268, 1448–1459.

Hengstler J.G. , Utesch D. , Steinberg P. , Platt K.L. , Diener B. , Ringel M. , Swales N. , Fischer T. , Biefang K. , Gerl M. , Bottger T. , & Oesch F. (2000). Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction. Drug Metabolism Reviews 32, 81–118.

LeCluyse E.L. (2001). Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. European Journal of Pharmaceutical Sciences 13, 343–368.

Wolf C.R. , & Smith G. (1999). Pharmacogenetics. British Medical Bulletin 55, 366–368.

Eaton D.L. , & Bammler T.K. (1999). Concise review of the glutathione S-transferases and their significance to toxicology. Toxicological Sciences 49, 156–164.

Burchell B. , Brierley C.H. , Monaghan G. , & Clarke D.J. (1998). The structure and function of the UDP-glucuronosyltransferase gene family. Advances in Pharmacology 42, 335–338.

Friedberg T. , Pritchard M.P. , Bandera M. , Hanlon S.P. , Yao D. , McLaughlin L.A. , Ding S. , Burchell B. , & Wolf C.R. (1999). Merits and limitations of recombinant models for the study of human P450-mediated drug metabolism and toxicity: an intralaboratory comparison. Drug Metabolism Reviews 31, 523–544.

White R.E. (2000). High-throughput screening in drug metabolism and pharmacokinetic support of drug discovery. Annual Review of Pharmacology and Toxicology 40, 133–157.

Clewell H.J. , & Andersen M.E. (1986). A multiple dose-route physiological model for volatile chemicals using ACSL/PC. In Languages for Continuous Simulation (ed. Cellier F.D. ). San Diego, CA, USA: Society for Computer Simulation.

Andersen M.E. (1991). Physiological modelling of organic compounds. Annals of Occupational Hygiene 35, 309–321.

Brown R.P. , Foran J. , Olin S. , & Robinson D. (1994). Physiological Parameter Values for PBPK Models, 100 pp. Washington, DC: International Life Sciences Institute (ILSI) Risk Science Institute (RSI).

Blaauboer B.J. , Forsby A. , Houston J.B. , Beckman M. , Combes R.D. , & DeJongh J. (2000). An integrated approach to the prediction of systemic toxicity using biokinetic models and biological in vitro test methods. In Progress in the Reduction, Refinement and Replacement of Animal Experimentation (ed. Balls M. , van Zeller A-M. , & Halder M.E. ), pp. 525–536. Amsterdam, The Netherlands: Elsevier.

Sato A. , & Nakajima T. (1979). A structure–activity relationship of some chlorinated hydrocarbons. Archives of Environmental Health 34, 69–75.

Perbellini L. , Brugnone F. , Caretta D. , & Maranelli G. (1985). Partition coefficients of some industrial aliphatic hydrocarbons (C₅–C₇) in blood and human tissues. British Journal of Industrial Medicine 42, 162–167.

Fiserova-Bergerova V. , & Diaz M.L. (1986). Determination and prediction of tissue-gas partition coefficients. International Archives of Occupational and Environmental Health 58, 75–87.

Pacifini G.M. , & Viani A. (1992). Methods of determining plasma and tissue binding of drugs. Clinical Pharmacokinetics 23, 449–468.

Jepson G.W. , Hoover D.K. , Black R.K. , McCafferty J.D. , Mahle D.A. , & Gearhart J.M. (1994). A partition coefficient determination method for nonvolatile chemicals in biological tissues. Fundamental and Applied Toxicology 22, 519–524.

DeJongh J. , Verhaar H.J. , & Hermens J.L. (1997). A quantitative property–property relationship (QPPR) approach to estimate in vitro tissue–blood partition coefficients of organic chemicals in rats and humans. Archives of Toxicology 72, 17–25.

DeJongh J. , Verhaar H.J.M. , & Hermens J.L.M. (1998). Role of kinetics in acute lethality of nonre-active volatile organic compounds (VOCs). Toxicological Science 45, 26–32.

Franke H. , Galla H. , & Beuckmann C.T. (2000). Primary cultures of brain microvessel endothelial cells: a valid and flexible model to study drug transport through the blood–brain barrier in vitro. Brain Research Protocols 5, 248–256.

Platts J.A. , Abraham M.H. , Hersey A. , & Butina D. (2000). Estimation of molecular linear free energy relationship descriptors. 4. Correlation and prediction of cell permeation. Pharmaceutical Research 17, 1013–1018.

Egan W.J. , Merz K.M. , & Baldwin J.J. (2000). Prediction of drug absorption using multivariate statistics. Journal of Medicinal Chemistry 43, 3867–3877.

Österberg T. , & Norinder U. (2000). Prediction of polar surface area and drug transport processes using simple parameters and PLS statistics. Journal of Chemical Information and Computer Sciences 40, 1408–1411.

Stenberg P. , Norinder U. , Luthman K. , & Artursson P. (2001). Experimental and computational screening models for the prediction of intestinal drug absorption. Journal of Medicinal Chemistry 44, 1927–1937.

Zhao Y.H. , Le J. , Abraham M.H. , Hersey A. , Eddershaw P.J. , Luscombe C.N. , Boutina D. , Beck G. , Sherborne B. , Cooper I. , & Platts J.A. (2001). Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure–activity relationship (QSAR) with the Abraham descriptors. Journal of Pharmaceutical Sciences 90, 749–784.

Barratt M.D. (1995). Quantitative structure–activity relationships for skin permeability. Toxicology in Vitro 9, 27–37.

Kirchner L.A. , Moody R.P. , Doyle E. , Bose R. , Jeffery J. , & Chu I. (1997). The prediction of skin permeability by using physicochemical data. ATLA 25, 359–370.

Worth A.P. , & Cronin M.T.D. (2000). Structure–permeability relationships for transcorneal penetration. ATLA 28, 403–413.

Clark D.E. , & Pickett S.D. (2000). Computational methods for the prediction of “drug-likeness”. Drug Discovery Today 5, 49–58.

Duffy J.C. , Cronin M.T.D. , Dearden J.C. , Moss G.P. , & Murray-Dickson G. (1999). Prediction of blood–brain barrier partitioning using QSAR analysis. Journal of Pharmacy and Pharmacology 51, Suppl. 1, 260.

Feher M. , Sourial E. , & Schmidt J.M. (2000). A simple model for the prediction of blood–brain partitioning. International Journal of Pharmaceutics 201, 239–247.

Agatonovic-Kustrin S. , Tucker I.G. , Zecevic M. , & Zivanovic L.J. (2000). Prediction of drug transfer into human milk from theoretically derived descriptors. Analytica Chimica Acta 418, 181–195.

Cronin M.T.D. , Dearden J.C. , Gupta R. , & Moss G.P. (1998). An investigation of the mechanism of flux across polydimethylsiloxane membranes by quantitative structure–permeability relationships. Journal of Pharmacy and Pharmacology 50, 143–152.