title: PK of immunoconjugate anticancer agent CMD-193 in rats: ligand-binding assay approach to determine in vivo immunoconjugate stability.
abstract: BACKGROUND
  Antibody-drug conjugates (ADCs) are a new generation of anticancer therapeutics. The objective of this manuscript is to propose a methodology that can be used to assess the stability of the ADCs by using the PK data obtained by ligand-binding assays that measure various components of ADCs.
  
  
  RESULTS
  The ligand-binding assays format of different components of ADCs provided unique valuable PK information. The mathematical manipulation of the bioanalytical data provided an insight into the in vivo integrity, indicating that the loading of the calicheamicin on the G193 antibody declines in an apparent slow first-order process.
  
  
  CONCLUSIONS
  This report demonstrates the value of analyzing various components of the ADC and their PK profiles to better understand the disposition and in vivo stability of ADCs.
authors.affiliation: Pharmacokinetic, Pharmacodynamics & Drug Metabolism, Merck Sharp & Dohme Corp., West Point, Pennsylvania, USA. azher_hussain@merck.com.
authors.forename: Azher
authors.initials: A
authors.lastname: Hussain
authors.forename: Boris
authors.initials: B
authors.lastname: Gorovits
authors.forename: Mauricio
authors.initials: M
authors.lastname: Leal
authors.forename: Eric
authors.initials: E
authors.lastname: Fluhler
mesh_terms: D000617:Aminoglycosides / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001681:Biological Assay; D004355:Drug Stability; D053281:Enediynes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D018796:Immunoconjugates / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D015233:Models, Statistical; D051381:Rats; D011994:Recombinant Proteins / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D053281:Enediynes; D018796:Immunoconjugates; D011994:Recombinant Proteins; C055955:calicheamicin gamma(1)I