PT  - JOURNAL ARTICLE
AU  - Pankaj Sethi
AU  - James V Bruckner
AU  - Tanzir Mortuza
AU  - Brian S Cummings
AU  - Srininvasa Muralidhara
AU  - Catherine A White
TI  - Plasma Protein and Lipoprotein Binding of cis- and trans-Permethrin and Deltamethrin in Adult Humans and Rats
AID  - 10.1124/dmd.118.085464
DP  - 2019 Jan 01
TA  - Drug Metabolism and Disposition
PG  - dmd.118.085464
4099  - http://dmd.aspetjournals.org/content/early/2019/06/27/dmd.118.085464.short
4100  - http://dmd.aspetjournals.org/content/early/2019/06/27/dmd.118.085464.full
AB  - The majority of residents of the U. S., Canada and Europe are exposed to pyrethroids, the most commonly used class of insecticides. Surprisingly little is known about key aspects of their pharmacokinetics, including their mode of transport in the systemic circulation. This study tested the hypothesis that pyrethroids are transported by both plasma lipoproteins and proteins, similarly to other highly lipophilic environmental contaminants. Other aims were to characterize the binding of representative Type I and II pyrethroids, and to compare their binding to rat versus human plasma. Binding of 14C-labeled cis- and trans-permethrin (CIS and TRANS) and deltamethrin (DLM) to proteins and lipoproteins was measured by sequential extraction of spiked plasma with isooctane, 2-octanol and acetonitrile. Binding of DLM, CIS and TRANS to plasma proteins and lipoproteins was linear from 250-750 nM, concentrations present in the plasma of orally dosed rats. Binding of DLM to high-density lipoprotein was twice that to low-density lipoprotein. Binding of DLM, CIS and TRANS was ~2-fold greater to proteins than to lipoproteins of rat and human plasma. Albumin was primarily responsible for protein binding. Higher total binding of each pyrethroid to human (~90%) than to rat (~80%) plasma resulted from higher protein binding in human plasma. This was attributable, in part to the higher albumin/protein content of human plasma. Rat albumin exhibited lower pyrethroid binding capacity than did human albumin. Results of this investigation indicate that albumin and lipoproteins play a major role in binding and transport of pyrethroids in the systemic circulation of both rats and humans.SIGNIFICANCE STATEMENT N/A