title: Bypassing nonparallelism of a monoclonal antibody ligand-binding assay by employment of alternative assay formats.
abstract: Determination of concentration-time profiles in cynomolgus monkeys of a therapeutic monoclonal antibody against a soluble target revealed a substantial discrepancy between a generic anti-human IgG capture/detection and target bridging assay with the target bridging assay leading to dose- and time-dependent underquantification of drug concentrations, lack of parallelism and subsequently different pharmacokinetic parameters. In contrast, plasma levels derived from a target capture and an anti-idiotypic antibody bridging assay were in close concordance with the generic assay and demonstrated parallelism with high precision across several dilutions. The results provide a practical attempt to overcome nonparallelism by employing alternative assay formats utilizing tailored assay reagent combinations in order to obtain unbiased pharmacokinetic data.
authors.affiliation: Bayer Pharma AG, Bioanalytics and Nonclinical Pharmacokinetics, Berlin and Wuppertal, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiesgen
authors.affiliation: Bayer Pharma AG, Bioanalytics and Nonclinical Pharmacokinetics, Berlin and Wuppertal, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Schröder
authors.affiliation: Bayer Pharma AG, Bioanalytics and Nonclinical Pharmacokinetics, Berlin and Wuppertal, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
authors.affiliation: Bayer Pharma AG, Outsourcing Management, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Czupalla
authors.affiliation: Bayer Pharma AG, Bioanalytics and Nonclinical Pharmacokinetics, Berlin and Wuppertal, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Braun
authors.affiliation: Bayer Pharma AG, Bioanalytics and Nonclinical Pharmacokinetics, Berlin and Wuppertal, Germany.
authors.forename: Mark Jean
authors.initials: MJ
authors.lastname: Gnoth
authors.affiliation: Bayer Pharma AG, Bioanalytics and Nonclinical Pharmacokinetics, Berlin and Wuppertal, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Grudzinska-Goebel
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000276:immunology / Q000493:pharmacokinetics; D019540:Area Under Curve; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006207:Half-Life; D008024:Ligands; D057230:Limit of Detection; D008252:Macaca fascicularis; D008297:Male; D015990:Placebo Effect; D012372:ROC Curve; D011817:Rabbits; D013997:Time Factors
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D008024:Ligands
keywords: anti-idiotypic antibody bridging assay; generic assay; lack of parallelism; ligand-binding assay; matrix interference; minimum required dilution; nonparallelism; soluble target; target bridging assay; target capture assay