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  • Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.

Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.

Drug metabolism and disposition: the biological fate of chemicals (2008-04-23)
R Scott Obach, Franco Lombardo, Nigel J Waters
ABSTRACT

We present herein a compilation and trend analysis of human i.v. pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data. This data set provides the drug metabolism scientist with a robust and accurate resource suitable for a number of applications, including in silico modeling, 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 i.v. 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 data set 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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Dichloroacetic acid, PESTANAL®, analytical standard
Supelco
Mebendazole, VETRANAL®, analytical standard
Supelco
Warfarin, PESTANAL®, analytical standard
Sigma-Aldrich
Phenacetin, ≥98.0% (HPLC)
Sigma-Aldrich
Erythromycin, tested according to Ph. Eur.
Supelco
Prednisolone, VETRANAL®, analytical standard
Supelco
Nitrofurantoin, VETRANAL®, analytical standard
Sigma-Aldrich
Dichloroacetic acid, ReagentPlus®, ≥99%
Sigma-Aldrich
2-Mercapto-1-methylimidazole, ≥99%
Sigma-Aldrich
Prednisolone, ≥99%
Sigma-Aldrich
17α-Ethynylestradiol, ≥98%
Supelco
(−)-Nicotine solution, 1.0 mg/mL, analytical standard, for drug analysis
Sigma-Aldrich
Prednisone, ≥98%
Sigma-Aldrich
Erythromycin, BioReagent, suitable for cell culture
Sigma-Aldrich
Erythromycin, meets USP testing specifications
Sigma-Aldrich
(−)-Nicotine, ≥99% (GC), liquid
Sigma-Aldrich
Lidocaine, powder
Sigma-Aldrich
Lidocaine, analytical standard
Sigma-Aldrich
7-(2,3-Dihydroxypropyl)theophylline
Sigma-Aldrich
Oxazepam
Sigma-Aldrich
Erythromycin, potency: ≥850 μg per mg
Sigma-Aldrich
Rifampicin, ≥95% (HPLC), powder or crystals
Supelco
Warfarin, analytical standard
Sigma-Aldrich
Rifampicin, suitable for plant cell culture, BioReagent, ≥95% (HPLC), powder or crystals
Supelco
D(−)-Norgestrel, analytical standard
Supelco
Mebendazole, analytical standard, ≥98% (HPLC)
Supelco
Digoxin, analytical standard
Sigma-Aldrich
Tetracycline, 98.0-102.0% (HPLC)
Sigma-Aldrich
Leuprolide acetate salt, ≥98% (HPLC)
Sigma-Aldrich
Nitrofurantoin, 98.0-102.0% (EP, UV)