PT - JOURNAL ARTICLE AU - Franco Lombardo AU - Giuliano Berellini AU - R. Scott Obach TI - TREND ANALYSIS OF A DATABASE OF INTRAVENOUS PHARMACOKINETIC PARAMETERS IN HUMANS FOR 1352 DRUG COMPOUNDS AID - 10.1124/dmd.118.082966 DP - 2018 Jan 01 TA - Drug Metabolism and Disposition PG - dmd.118.082966 4099 - http://dmd.aspetjournals.org/content/early/2018/08/16/dmd.118.082966.short 4100 - http://dmd.aspetjournals.org/content/early/2018/08/16/dmd.118.082966.full AB - We report a compilation and trend analysis of human intravenous pharmacokinetic data on 1352 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data. The aim in building this dataset and its detailed analysis was to provide, as in the previous case published in 2008, an extended, robust and accurate resource which could be applied by drug metabolism, clinical pharmacology and medicinal chemistry scientists to in silico modeling, in vitro - in vivo scaling, and physiologically-based pharmacokinetic approaches. All in vivo data were obtained or derived from original references, either through literature or regulatory agencies reports, exclusively from studies utilizing intravenous administration. Plasma protein binding data were collected from other available sources to supplement these pharmacokinetic data. These parameters were analyzed concurrently with a range of physicochemical properties and resultant trends and patterns within the data are presented. In addition, the date of first disclosure of each molecule was reported and the potential "temporal" impact on data trends was analyzed. Our findings with this much expanded dataset were consistent with earlier described notions of trends between physicochemical properties and pharmacokinetic behavior. These observations and analyses, along with the large database of human pharmacokinetic data, should enable future efforts aimed toward developing quantitative structure-pharmacokinetic relationships and improving our understanding of the relationship between fundamental chemical characteristics and drug disposition.