Judith A Herlich, Peter Taggart, Jim Proctor, Paul Stahle, Rolland Colis, LeRoy Hall, Michael K Pugsley
{"title":"非glp耐受性/剂量范围发现研究:早期毒理学筛选项目的设计和方法。","authors":"Judith A Herlich, Peter Taggart, Jim Proctor, Paul Stahle, Rolland Colis, LeRoy Hall, Michael K Pugsley","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>A major directive of Pharmaceutical Research and Development (R&D) is to efficiently advance potential new chemical entities (NCEs) from the Discovery therapeutic area into Global Preclinical Development (GPCD), where a safety profile can be established. To facilitate the transition a comprehensive toxicity evaluation is required. In order to support both the R&D Discovery teams and GPCD, investigative (non-GLP) tolerance/dose range finding studies are conducted. These studies are designed to provide a quality toxicological and toxicokinetic assessment of potential NCEs early in the drug development process. During tolerance evaluations, compounds are first assessed in a single dose escalation (SDE) phase where rodents (or canines) receive a single dose anticipated to achieve relevant multiples of the efficacious dose. Data from this phase evaluates NCE absorption, and assists in estimating the maximum tolerated dose for a single administration and establish doses for a repeat dose (RD) phase. Data from the RD phase are used to determine potential target tissues of toxicity and also select doses for future GLP Toxicology studies. Thus, a rapid assessment of the toxicological profile of the NCE can be made to establish initial safety facilitating conduct of subsequent regulatory Toxicological studies and potentially earlier entry into clinical trials.</p>","PeriodicalId":20701,"journal":{"name":"Proceedings of the Western Pharmacology Society","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The non-GLP toleration/dose range finding study: design and methodology used in an early toxicology screening program.\",\"authors\":\"Judith A Herlich, Peter Taggart, Jim Proctor, Paul Stahle, Rolland Colis, LeRoy Hall, Michael K Pugsley\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>A major directive of Pharmaceutical Research and Development (R&D) is to efficiently advance potential new chemical entities (NCEs) from the Discovery therapeutic area into Global Preclinical Development (GPCD), where a safety profile can be established. To facilitate the transition a comprehensive toxicity evaluation is required. In order to support both the R&D Discovery teams and GPCD, investigative (non-GLP) tolerance/dose range finding studies are conducted. These studies are designed to provide a quality toxicological and toxicokinetic assessment of potential NCEs early in the drug development process. During tolerance evaluations, compounds are first assessed in a single dose escalation (SDE) phase where rodents (or canines) receive a single dose anticipated to achieve relevant multiples of the efficacious dose. Data from this phase evaluates NCE absorption, and assists in estimating the maximum tolerated dose for a single administration and establish doses for a repeat dose (RD) phase. Data from the RD phase are used to determine potential target tissues of toxicity and also select doses for future GLP Toxicology studies. Thus, a rapid assessment of the toxicological profile of the NCE can be made to establish initial safety facilitating conduct of subsequent regulatory Toxicological studies and potentially earlier entry into clinical trials.</p>\",\"PeriodicalId\":20701,\"journal\":{\"name\":\"Proceedings of the Western Pharmacology Society\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2009-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Proceedings of the Western Pharmacology Society\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the Western Pharmacology Society","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
The non-GLP toleration/dose range finding study: design and methodology used in an early toxicology screening program.
A major directive of Pharmaceutical Research and Development (R&D) is to efficiently advance potential new chemical entities (NCEs) from the Discovery therapeutic area into Global Preclinical Development (GPCD), where a safety profile can be established. To facilitate the transition a comprehensive toxicity evaluation is required. In order to support both the R&D Discovery teams and GPCD, investigative (non-GLP) tolerance/dose range finding studies are conducted. These studies are designed to provide a quality toxicological and toxicokinetic assessment of potential NCEs early in the drug development process. During tolerance evaluations, compounds are first assessed in a single dose escalation (SDE) phase where rodents (or canines) receive a single dose anticipated to achieve relevant multiples of the efficacious dose. Data from this phase evaluates NCE absorption, and assists in estimating the maximum tolerated dose for a single administration and establish doses for a repeat dose (RD) phase. Data from the RD phase are used to determine potential target tissues of toxicity and also select doses for future GLP Toxicology studies. Thus, a rapid assessment of the toxicological profile of the NCE can be made to establish initial safety facilitating conduct of subsequent regulatory Toxicological studies and potentially earlier entry into clinical trials.