title: Measurement of plasma protein and lipoprotein binding of pyrethroids.
abstract: BACKGROUND
  A simple, reliable procedure was developed to measure binding of pyrethroid insecticides to total proteins and lipoproteins of rat and human plasma.
  
  
  METHODS
  The extent of binding of (14)C-labeled deltamethrin (DLM), cis-permethrin (CIS) and trans-permethrin (TRANS) was quantified by a 3-step organic solvent extraction technique. Rat and human plasma samples, containing NaF to inhibit esterases, were spiked with a range of concentrations of each radiolabeled pyrethroid. Protein binding reached equilibrium within ~1h of incubation at 37°C. The samples were extracted in turn with: isooctane to collect the unbound fraction; 2-octanol to extract the lipoprotein-bound fraction; and acetonitrile to obtain the protein-bound fraction.
  
  
  RESULTS
  Absolute recoveries of DLM, CIS and TRANS ranged from 86 to 95%. Adherence of these very lipophilic chemicals to glass and plastic was minimized by using silanized glass vials and LoBind® plastic pipettes. The method's ability to distinguish lipoprotein from protein binding was confirmed by experiments with diazepam and cyclosporine, drugs that bind selectively to albumin and lipoproteins, respectively.
  
  
  CONCLUSIONS
  This procedure was effectively utilized for studies of the species-dependence of plasma protein and lipoprotein binding of three pyrethroids for inclusion in physiologically-based pharmacokinetic models of pyrethroids for use in health risk assessments of the insecticides in children and adults.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2354, USA. Electronic address: pankaj.uga@gmail.com.
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Sethi
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2354, USA. Electronic address: smuralidhara@rx.uga.edu.
authors.forename: S
authors.initials: S
authors.lastname: Muralidhara
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2354, USA. Electronic address: bruckner@rx.uga.edu.
authors.forename: James V
authors.initials: JV
authors.lastname: Bruckner
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2354, USA. Electronic address: cwhite@rx.uga.edu.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: White
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000737:chemistry*; D002250:Carbon Radioisotopes / Q000097:blood; D016572:Cyclosporine / Q000737:chemistry; D003975:Diazepam / Q000737:chemistry; D006801:Humans; D007306:Insecticides / Q000097:blood / Q000737:chemistry; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry*; D009570:Nitriles / Q000097:blood / Q000737:chemistry; D000442:Octanols / Q000737:chemistry; D026023:Permethrin / Q000097:blood / Q000737:chemistry; D010949:Plasma / Q000737:chemistry*; D011485:Protein Binding; D011722:Pyrethrins / Q000097:blood* / Q000737:chemistry*; D011869:Radioligand Assay / Q000379:methods*; D051381:Rats; D018570:Risk Assessment
chemical_list: D001798:Blood Proteins; D002250:Carbon Radioisotopes; D007306:Insecticides; D008074:Lipoproteins; D009570:Nitriles; D000442:Octanols; D011722:Pyrethrins; C017180:decamethrin; D026023:Permethrin; C067943:2-octanol; D016572:Cyclosporine; D003975:Diazepam
keywords: Binding; Cyclosporine binding; Deltamethrin; Diazepam binding; Lipoproteins; Method; Permethrin; Plasma proteins; Pyrethroid; Solvent extraction