Received for publication January 16, 2008.
Revised April 18, 2008.
Accepted for publication April 18, 2008.

TREND ANALYSIS OF A DATABASE OF INTRAVENOUS PHARMACOKINETIC PARAMETERS IN HUMANS FOR 670 DRUG COMPOUNDS

Abstract

We present herein a compilation and trend analysis of human intravenous pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data. This dataset provides the drug metabolism scientist with a robust and accurate resource suitable for a number of applications including: in silico modelling, in vitro - in vivo scaling, and physiologically-based pharmacokinetic approaches. Clearance, volume of distribution at steady state, mean residence time, and terminal phase half-life were obtained or derived from original references exclusively from studies utilizing intravenous administration. Plasma protein binding data were collected from other sources to supplement these pharmacokinetic data. These parameters were analyzed concurrently with a range of simple physicochemical descriptors and resultant trends and patterns within the data are presented. 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.

Key words: clinical pharmacokinetics, drug discovery, human pharmacokinetics, mean residence time, plasma protein binding