{"id":"https://openalex.org/W75804964","doi":"https://doi.org/10.1016/b0-08-045044-x/00154-1","title":"Mechanism-Based Pharmacokinetic\u2013Pharmacodynamic Modeling for the Prediction of In Vivo Drug Concentration\u2013Effect Relationships \u2013 Application in Drug Candidate Selection and Lead Optimization","display_name":"Mechanism-Based Pharmacokinetic\u2013Pharmacodynamic Modeling for the Prediction of In Vivo Drug Concentration\u2013Effect Relationships \u2013 Application in Drug Candidate Selection and Lead Optimization","publication_year":2007,"publication_date":"2007-01-01","ids":{"openalex":"https://openalex.org/W75804964","doi":"https://doi.org/10.1016/b0-08-045044-x/00154-1","mag":"75804964"},"language":"en","primary_location":{"id":"doi:10.1016/b0-08-045044-x/00154-1","doi":"https://doi.org/10.1016/b0-08-045044-x/00154-1","is_oa":false,"landing_page_url":"https://doi.org/10.1016/b0-08-045044-x/00154-1","pdf_url":null,"source":{"id":"https://openalex.org/S4306463230","display_name":"Elsevier eBooks","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"ebook platform"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Comprehensive Medicinal Chemistry II","raw_type":"book-chapter"},"volume":null,"type":"book-chapter","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5033133140","display_name":"Meindert Danhof","orcid":"https://orcid.org/0000-0002-2319-6830","observed_orcids":["https://orcid.org/0000-0002-2319-6830"]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"M. Danhof","raw_affiliation_strings":["Leiden University, Leiden, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden University, Leiden, The Netherlands","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077172862","display_name":"Piet H. van der Graaf","orcid":"https://orcid.org/0000-0003-1314-3484","observed_orcids":["https://orcid.org/0000-0003-1314-3484"]},"institutions":[{"id":"https://openalex.org/I189718659","display_name":"Pfizer (United Kingdom)","ror":"https://ror.org/04x4v8p40","country_code":"GB","type":"company","lineage":["https://openalex.org/I180857899","https://openalex.org/I189718659"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"P.H. Van der Graaf","raw_affiliation_strings":["Pfizer Global Research and Development, Sandwich, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pfizer Global Research and Development, Sandwich, UK","institution_ids":["https://openalex.org/I189718659"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008224959","display_name":"Dani\u00ebl Martijn Jonker","orcid":"https://orcid.org/0000-0002-8227-9361","observed_orcids":["https://orcid.org/0000-0002-8227-9361"]},"institutions":[{"id":"https://openalex.org/I189090001","display_name":"Novo Nordisk (Denmark)","ror":"https://ror.org/0435rc536","country_code":"DK","type":"company","lineage":["https://openalex.org/I189090001","https://openalex.org/I2801134892","https://openalex.org/I4210159963"]}],"countries":["DK"],"is_corresponding":false,"raw_author_name":"D.M. Jonker","raw_affiliation_strings":["Novo Nordisk A/S, Bagsv aelig;rd, Denmark","Novo Nordisk A/S, Bagsv aelig","rd, Denmark"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Novo Nordisk A/S, Bagsv aelig;rd, Denmark","institution_ids":["https://openalex.org/I189090001"]},{"raw_affiliation_string":"Novo Nordisk A/S, Bagsv aelig","institution_ids":["https://openalex.org/I189090001"]},{"raw_affiliation_string":"rd, Denmark","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046857648","display_name":"Sandra A. G. Visser","orcid":"https://orcid.org/0009-0008-2186-7195","observed_orcids":["https://orcid.org/0009-0008-2186-7195"]},"institutions":[{"id":"https://openalex.org/I4210143795","display_name":"AstraZeneca (Sweden)","ror":"https://ror.org/04wwrrg31","country_code":"SE","type":"company","lineage":["https://openalex.org/I105036370","https://openalex.org/I4210143795"]}],"countries":["SE"],"is_corresponding":false,"raw_author_name":"S.A.G. Visser","raw_affiliation_strings":["AstraZeneca R&D, S\u00f6dert\u00e4lje, Sweden"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"AstraZeneca R&D, S\u00f6dert\u00e4lje, Sweden","institution_ids":["https://openalex.org/I4210143795"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5032960345","display_name":"Klaas P. Zuideveld","orcid":"https://orcid.org/0009-0009-9631-033X","observed_orcids":["https://orcid.org/0009-0009-9631-033X"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"K.P. Zuideveld","raw_affiliation_strings":["F. Hoffmann-La Roche Ltd, Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"F. Hoffmann-La Roche Ltd, Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]}],"institutions":[],"countries_distinct_count":5,"institutions_distinct_count":5,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":6.5619,"has_fulltext":false,"cited_by_count":13,"citation_normalized_percentile":{"value":0.96827411,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":97},"biblio":{"volume":null,"issue":null,"first_page":"885","last_page":"908"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11235","display_name":"Statistical Methods in Clinical Trials","score":0.7143999934196472,"subfield":{"id":"https://openalex.org/subfields/2613","display_name":"Statistics and Probability"},"field":{"id":"https://openalex.org/fields/26","display_name":"Mathematics"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11235","display_name":"Statistical Methods in Clinical Trials","score":0.7143999934196472,"subfield":{"id":"https://openalex.org/subfields/2613","display_name":"Statistics and Probability"},"field":{"id":"https://openalex.org/fields/26","display_name":"Mathematics"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T12547","display_name":"Pharmaceutical studies and practices","score":0.11159999668598175,"subfield":{"id":"https://openalex.org/subfields/2735","display_name":"Pediatrics, Perinatology and Child Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.08900000154972076,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/drug-concentration-effect-relationship","display_name":"drug concentration-effect relationship","score":0.7300000190734863},{"id":"https://openalex.org/keywords/drug-candidate-selection","display_name":"drug candidate selection","score":0.847000002861023},{"id":"https://openalex.org/keywords/lead-optimization","display_name":"lead optimization","score":0.9980000257492065},{"id":"https://openalex.org/keywords/pharmacodynamic-endpoints","display_name":"pharmacodynamic endpoints","score":0.5669999718666077},{"id":"https://openalex.org/keywords/biomarkers","display_name":"biomarkers","score":0.8519999980926514},{"id":"https://openalex.org/keywords/receptor-binding-affinity","display_name":"receptor binding affinity","score":0.6650000214576721},{"id":"https://openalex.org/keywords/intrinsic-efficacy","display_name":"intrinsic efficacy","score":0.9309999942779541},{"id":"https://openalex.org/keywords/homeostatic-feedback","display_name":"homeostatic feedback","score":0.7179999947547913},{"id":"https://openalex.org/keywords/adenosine-a1-receptor-agonist","display_name":"adenosine A1 receptor agonist","score":0.9490000009536743},{"id":"https://openalex.org/keywords/mu-opioid-receptor-agonists","display_name":"mu-opioid receptor agonists","score":0.9599999785423279},{"id":"https://openalex.org/keywords/gaba-a-receptor-agonists","display_name":"GABA-A receptor agonists","score":0.9980000257492065},{"id":"https://openalex.org/keywords/qt-interval-prolongation","display_name":"QT prolongation","score":0.878000020980835},{"id":"https://openalex.org/keywords/preclinical-drug-development","display_name":"preclinical drug development","score":0.5910000205039978},{"id":"https://openalex.org/keywords/in-vitro-in-vivo-extrapolation","display_name":"in vitro-in vivo extrapolation","score":0.6449999809265137}],"concepts":[{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.6369613409042358},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6361244320869446},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.6246132850646973},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.5906000137329102},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.5513564944267273},{"id":"https://openalex.org/C64903051","wikidata":"https://www.wikidata.org/wiki/Q2198549","display_name":"Drug development","level":3,"score":0.5223254561424255},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.5095468163490295},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.5006678104400635},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4484614133834839},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.34347742795944214},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.2821950316429138},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.21669906377792358},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.07937806844711304},{"id":"https://openalex.org/C111472728","wikidata":"https://www.wikidata.org/wiki/Q9471","display_name":"Epistemology","level":1,"score":0.0},{"id":"https://openalex.org/C138885662","wikidata":"https://www.wikidata.org/wiki/Q5891","display_name":"Philosophy","level":0,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1016/b0-08-045044-x/00154-1","doi":"https://doi.org/10.1016/b0-08-045044-x/00154-1","is_oa":false,"landing_page_url":"https://doi.org/10.1016/b0-08-045044-x/00154-1","pdf_url":null,"source":{"id":"https://openalex.org/S4306463230","display_name":"Elsevier eBooks","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"ebook platform"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Comprehensive Medicinal Chemistry II","raw_type":"book-chapter"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9391000270843506,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":116,"referenced_works":["https://openalex.org/W48496034","https://openalex.org/W261464235","https://openalex.org/W1479954283","https://openalex.org/W1495834546","https://openalex.org/W1516221483","https://openalex.org/W1531492147","https://openalex.org/W1535180370","https://openalex.org/W1537977205","https://openalex.org/W1558293110","https://openalex.org/W1569491953","https://openalex.org/W1908131908","https://openalex.org/W1940342907","https://openalex.org/W1942398841","https://openalex.org/W1963748793","https://openalex.org/W1963933839","https://openalex.org/W1966872254","https://openalex.org/W1969683921","https://openalex.org/W1972658106","https://openalex.org/W1974705367","https://openalex.org/W1979836689","https://openalex.org/W1982438938","https://openalex.org/W1982625493","https://openalex.org/W1983635800","https://openalex.org/W1983693956","https://openalex.org/W1985086317","https://openalex.org/W1986394666","https://openalex.org/W1988062492","https://openalex.org/W1988360351","https://openalex.org/W1988835089","https://openalex.org/W1990804906","https://openalex.org/W1992131299","https://openalex.org/W1997967494","https://openalex.org/W2003883797","https://openalex.org/W2005332203","https://openalex.org/W2005747290","https://openalex.org/W2008492335","https://openalex.org/W2009087137","https://openalex.org/W2012005822","https://openalex.org/W2012293219","https://openalex.org/W2013613063","https://openalex.org/W2015901089","https://openalex.org/W2019298705","https://openalex.org/W2024951267","https://openalex.org/W2027733032","https://openalex.org/W2027877139","https://openalex.org/W2028351745","https://openalex.org/W2031825791","https://openalex.org/W2034456133","https://openalex.org/W2036613133","https://openalex.org/W2037342295","https://openalex.org/W2037824865","https://openalex.org/W2042642523","https://openalex.org/W2043133079","https://openalex.org/W2044239953","https://openalex.org/W2048706813","https://openalex.org/W2049162091","https://openalex.org/W2053488031","https://openalex.org/W2056127650","https://openalex.org/W2056978517","https://openalex.org/W2061720918","https://openalex.org/W2066482395","https://openalex.org/W2067770236","https://openalex.org/W2068936181","https://openalex.org/W2075151761","https://openalex.org/W2078380224","https://openalex.org/W2079445105","https://openalex.org/W2080822597","https://openalex.org/W2084721137","https://openalex.org/W2087759076","https://openalex.org/W2091648211","https://openalex.org/W2106059095","https://openalex.org/W2106861254","https://openalex.org/W2107065429","https://openalex.org/W2109100173","https://openalex.org/W2109392677","https://openalex.org/W2113927644","https://openalex.org/W2115481607","https://openalex.org/W2115682190","https://openalex.org/W2115707323","https://openalex.org/W2115780912","https://openalex.org/W2126561556","https://openalex.org/W2128338810","https://openalex.org/W2129384252","https://openalex.org/W2130792137","https://openalex.org/W2135578299","https://openalex.org/W2139629662","https://openalex.org/W2140113414","https://openalex.org/W2140458881","https://openalex.org/W2140833549","https://openalex.org/W2141230342","https://openalex.org/W2142667771","https://openalex.org/W2151491015","https://openalex.org/W2154799399","https://openalex.org/W2156460167","https://openalex.org/W2157722031","https://openalex.org/W2160534829","https://openalex.org/W2163121088","https://openalex.org/W2166318615","https://openalex.org/W2169533599","https://openalex.org/W2170326611","https://openalex.org/W2171129696","https://openalex.org/W2171756360","https://openalex.org/W2211245678","https://openalex.org/W2217465947","https://openalex.org/W2242919303","https://openalex.org/W2266970241","https://openalex.org/W2279175373","https://openalex.org/W2293514211","https://openalex.org/W2312088836","https://openalex.org/W2324227497","https://openalex.org/W4230381786","https://openalex.org/W4233418772","https://openalex.org/W4252701457","https://openalex.org/W4256317982","https://openalex.org/W4406057208","https://openalex.org/W4406059090"],"related_works":["https://openalex.org/W7098724458","https://openalex.org/W2154180317","https://openalex.org/W2076472674","https://openalex.org/W7172531688","https://openalex.org/W2102456247","https://openalex.org/W2088206004","https://openalex.org/W4393153657","https://openalex.org/W1990804906","https://openalex.org/W2018451350","https://openalex.org/W1986672593"],"abstract_inverted_index":null,"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":3}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}
