{"id":"https://openalex.org/W2007702625","doi":"https://doi.org/10.1111/1755-5922.12022","title":"Age and Sex Effects on the Single\u2010 and Multiple\u2010Dose Safety and Pharmacokinetics of the New Renin Inhibitor ACT \u2010178882","display_name":"Age and Sex Effects on the Single\u2010 and Multiple\u2010Dose Safety and Pharmacokinetics of the New Renin Inhibitor ACT \u2010178882","publication_year":2013,"publication_date":"2013-01-11","ids":{"openalex":"https://openalex.org/W2007702625","doi":"https://doi.org/10.1111/1755-5922.12022","mag":"2007702625","pmid":"https://pubmed.ncbi.nlm.nih.gov/23311732"},"language":"en","primary_location":{"id":"doi:10.1111/1755-5922.12022","doi":"https://doi.org/10.1111/1755-5922.12022","is_oa":true,"landing_page_url":"https://doi.org/10.1111/1755-5922.12022","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1755-5922.12022","source":{"id":"https://openalex.org/S73613154","display_name":"Cardiovascular Therapeutics","issn_l":"1755-5914","issn":["1755-5914","1755-5922"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cardiovascular Therapeutics","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1755-5922.12022","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5058093690","display_name":"Jasper Dingemanse","orcid":"https://orcid.org/0000-0002-4083-5817","observed_orcids":["https://orcid.org/0000-0002-4083-5817"]},"institutions":[{"id":"https://openalex.org/I95056601","display_name":"Actelion (Switzerland)","ror":"https://ror.org/001yedb91","country_code":"CH","type":"company","lineage":["https://openalex.org/I95056601"]}],"countries":["CH"],"is_corresponding":true,"raw_author_name":"Jasper Dingemanse","raw_affiliation_strings":["Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland","institution_ids":["https://openalex.org/I95056601"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5103501686","display_name":"Laurent B. Nicolas","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I95056601","display_name":"Actelion (Switzerland)","ror":"https://ror.org/001yedb91","country_code":"CH","type":"company","lineage":["https://openalex.org/I95056601"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Laurent Nicolas","raw_affiliation_strings":["Department of Clinical Pharmacology Actelion Pharmaceuticals Ltd Allschwil Switzerland","Actelion Pharmaceuticals Ltd Department of Clinical Pharmacology Allschwil Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Clinical Pharmacology Actelion Pharmaceuticals Ltd Allschwil Switzerland","institution_ids":["https://openalex.org/I95056601"]},{"raw_affiliation_string":"Actelion Pharmaceuticals Ltd Department of Clinical Pharmacology Allschwil Switzerland","institution_ids":["https://openalex.org/I95056601"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5058093690"],"corresponding_institution_ids":["https://openalex.org/I95056601"],"apc_list":{"value":2160,"currency":"USD","value_usd":2160},"apc_paid":null,"fwci":0.6544,"has_fulltext":true,"cited_by_count":3,"citation_normalized_percentile":{"value":0.73399758,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":93},"biblio":{"volume":"31","issue":"5","first_page":"307","last_page":"313"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11001","display_name":"Renin-Angiotensin System Studies","score":0.8672000169754028,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11001","display_name":"Renin-Angiotensin System Studies","score":0.8672000169754028,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"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/T12547","display_name":"Pharmaceutical studies and practices","score":0.051100000739097595,"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/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.01759999990463257,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"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/renin-inhibitors","display_name":"renin inhibitors","score":0.796999990940094},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.8339999914169312},{"id":"https://openalex.org/keywords/age-effects","display_name":"age effects","score":0.843999981880188},{"id":"https://openalex.org/keywords/sex-differences","display_name":"sex differences","score":0.9179999828338623},{"id":"https://openalex.org/keywords/elderly-patients","display_name":"elderly patients","score":0.7009999752044678},{"id":"https://openalex.org/keywords/dose-proportionality","display_name":"dose proportionality","score":0.8029999732971191},{"id":"https://openalex.org/keywords/diarrhea","display_name":"diarrhea","score":0.5130000114440918},{"id":"https://openalex.org/keywords/drug-safety","display_name":"drug safety","score":0.7360000014305115},{"id":"https://openalex.org/keywords/dose-adjustment","display_name":"dose adjustment","score":0.6449999809265137}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.9513429403305054},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.8247994184494019},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.5370150804519653},{"id":"https://openalex.org/C198710026","wikidata":"https://www.wikidata.org/wiki/Q898218","display_name":"Renin\u2013angiotensin system","level":3,"score":0.47119495272636414},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.35540056228637695},{"id":"https://openalex.org/C84393581","wikidata":"https://www.wikidata.org/wiki/Q82642","display_name":"Blood pressure","level":2,"score":0.11219403147697449}],"mesh":[{"descriptor_ui":"D000092502","descriptor_name":"Renin Inhibitors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000293","descriptor_name":"Adolescent","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000367","descriptor_name":"Age Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000368","descriptor_name":"Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000369","descriptor_name":"Aged, 80 and over","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003521","descriptor_name":"Cyclopropanes","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D003521","descriptor_name":"Cyclopropanes","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D003521","descriptor_name":"Cyclopropanes","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D004311","descriptor_name":"Double-Blind Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011725","descriptor_name":"Pyridines","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D011725","descriptor_name":"Pyridines","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D011725","descriptor_name":"Pyridines","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D012737","descriptor_name":"Sex Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1111/1755-5922.12022","doi":"https://doi.org/10.1111/1755-5922.12022","is_oa":true,"landing_page_url":"https://doi.org/10.1111/1755-5922.12022","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1755-5922.12022","source":{"id":"https://openalex.org/S73613154","display_name":"Cardiovascular Therapeutics","issn_l":"1755-5914","issn":["1755-5914","1755-5922"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cardiovascular Therapeutics","raw_type":"journal-article"},{"id":"pmid:23311732","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/23311732","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cardiovascular therapeutics","raw_type":"Clinical Trial"}],"best_oa_location":{"id":"doi:10.1111/1755-5922.12022","doi":"https://doi.org/10.1111/1755-5922.12022","is_oa":true,"landing_page_url":"https://doi.org/10.1111/1755-5922.12022","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1755-5922.12022","source":{"id":"https://openalex.org/S73613154","display_name":"Cardiovascular Therapeutics","issn_l":"1755-5914","issn":["1755-5914","1755-5922"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cardiovascular Therapeutics","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":1.0}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320338282","display_name":"Actelion Pharmaceuticals","ror":"https://ror.org/001yedb91"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2007702625.pdf","grobid_xml":"https://content.openalex.org/works/W2007702625.grobid-xml"},"referenced_works_count":25,"referenced_works":["https://openalex.org/W71275700","https://openalex.org/W1556631311","https://openalex.org/W1892429132","https://openalex.org/W1971567116","https://openalex.org/W1978599196","https://openalex.org/W1982392960","https://openalex.org/W1986316858","https://openalex.org/W1996395903","https://openalex.org/W1996952253","https://openalex.org/W2029292711","https://openalex.org/W2041059138","https://openalex.org/W2065803736","https://openalex.org/W2086976847","https://openalex.org/W2093325995","https://openalex.org/W2106012731","https://openalex.org/W2108964268","https://openalex.org/W2121754021","https://openalex.org/W2131656660","https://openalex.org/W2133211347","https://openalex.org/W2137177722","https://openalex.org/W2137772241","https://openalex.org/W2149485684","https://openalex.org/W2154579091","https://openalex.org/W2166802777","https://openalex.org/W2408348716"],"related_works":["https://openalex.org/W2010545688","https://openalex.org/W2035577898","https://openalex.org/W2126325398","https://openalex.org/W2065803736","https://openalex.org/W2068697664","https://openalex.org/W2003731085","https://openalex.org/W1993114157","https://openalex.org/W1491002974","https://openalex.org/W2111922465","https://openalex.org/W2138088146"],"abstract_inverted_index":{"AIM:":[0],"To":[1],"investigate":[2],"the":[3,10,26,31,49,55,81,87,131,205,208],"effect":[4],"of":[5,17,30,44,54,95,109,136,186,224],"age":[6,166,243],"and":[7,12,15,35,38,60,78,89,100,134,141,153,204,221],"sex":[8,200,234],"on":[9,233,242],"single-":[11,88,220],"multiple-dose":[13,90,180,222],"safety":[14],"pharmacokinetics":[16],"ACT-178882,":[18],"a":[19,42,238],"new":[20],"direct":[21],"renin":[22],"inhibitor.":[23],"METHODS:":[24],"In":[25,48,130,164],"single-dose,":[27],"open-label":[28],"part":[29,53,133],"study,":[32,56],"healthy":[33,57],"young":[34,151],"elderly":[36,58,148,183],"male":[37,59,177],"female":[39,61,175],"subjects":[40,62,103],"received":[41,63],"dose":[43,98,212,216,230,239],"300":[45],"mg":[46],"ACT-178882.":[47],"multiple-dose,":[50],"double-blind,":[51],"placebo-controlled":[52],"ACT-178882":[64,110,169,187,225],"(300":[65],"or":[66,69,127],"600":[67],"mg)":[68],"placebo":[70,102],"once-a-day":[71],"for":[72,139],"14":[73],"days.":[74],"RESULTS:":[75],"Mild":[76],"headache":[77],"diarrhea":[79,96],"were":[80,143,171,202],"most":[82],"common":[83],"adverse":[84,106],"events":[85],"in":[86,114,119,147,174,207],"parts,":[91],"respectively.":[92],"The":[93],"frequency":[94],"increased":[97],"dependently,":[99],"no":[101],"reported":[104],"this":[105],"event.":[107],"Administration":[108],"did":[111],"not":[112],"result":[113],"any":[115],"clinically":[116],"relevant":[117],"changes":[118],"ECG,":[120],"vial":[121],"signs,":[122],"clinical":[123],"laboratory,":[124],"body":[125],"weight,":[126],"physical":[128],"examination.":[129],"single-dose":[132,198],"independent":[135],"sex,":[137],"values":[138],"Cmax":[140],"AUC0-\u221e":[142],"about":[144,156,190],"85%":[145],"higher":[146,173],"compared":[149,196],"with":[150,197,210],"subjects,":[152,184],"t1/2":[154,192],"was":[155,188,193,226],"5":[157],"h":[158],"longer":[159],"(29.3":[160],"vs.":[161],"24.1":[162],"h).":[163],"both":[165],"groups,":[167],"plasma":[168],"concentrations":[170],"slightly":[172],"versus":[176],"subjects.":[178],"Following":[179],"administration":[181,223],"to":[182],"accumulation":[185],"moderate,":[189],"1.8-fold,":[191],"unchanged":[194],"as":[195],"administration,":[199],"effects":[201],"minimal,":[203],"increase":[206],"exposure":[209],"increasing":[211],"appeared":[213],"less":[214],"than":[215],"proportional.":[217],"CONCLUSION:":[218],"Overall,":[219],"well":[227],"tolerated.":[228],"No":[229],"adaptation":[231],"based":[232,241],"is":[235],"necessary,":[236],"whereas":[237],"reduction":[240],"could":[244],"be":[245],"considered.":[246]},"counts_by_year":[{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}