title: Competitive particle concentration fluorescence immunoassays for measuring anti-diabetic drug levels in mouse plasma.
abstract: Two competitive particle concentration fluorescence immunoassays were developed to measure blood levels of analogs of anti-diabetic drugs being tested in diabetic mice. Ligands that contained the active pharmacophores were conjugated to PPD for immunization and to beta-phycoerythrin for use as a tracer in the immunoassays. Approximately 90% of 262 compounds assayed were detectable at less than 120 nM in plasma which was well below the estimated therapeutic level of 1 microM for lowering blood glucose. These data were used to define the bioavailability of test compounds and assist in decisions of constructing active analogs. Of additional interest, we noted crossreactivity of one monoclonal antibody for 3 different compound classes that are all known to bind with varying affinities to peroxisome proliferator-activated receptors.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. bright_stuart@lilly.com
authors.forename: S W
authors.initials: SW
authors.lastname: Bright
authors.forename: F C
authors.initials: FC
authors.lastname: Tinsley
authors.forename: S J
authors.initials: SJ
authors.lastname: Dominianni
authors.forename: K K
authors.initials: KK
authors.lastname: Schmiegel
authors.forename: L L
authors.initials: LL
authors.lastname: Fitch
authors.forename: G
authors.initials: G
authors.lastname: Gold
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001682:Biological Availability; D002839:Chromans / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods*; D005453:Fluorescence; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007118:Immunoassay / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010799:Phycoerythrin / Q000276:immunology; D013844:Thiazoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D045162:Thiazolidinediones; D000077288:Troglitazone; D014373:Tuberculin / Q000276:immunology
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D014373:Tuberculin; D010799:Phycoerythrin; D000077288:Troglitazone; D005947:Glucose