Canine Albumin Polymorphisms and Their Impact on Drug Plasma Protein Binding

• Published in: Drug metabolism and disposition Vol. 47; no. 10; pp. 1024 - 1031
• Main Authors: Costa, Ana P., Court, Michael H., Burke, Neal S., Zhu, Zhaohui, Mealey, Katrina L., Villarino, Nicolas F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019; American Society for Pharmacology and Experimental Therapeutics, Inc; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: Albumin; Albumins; Alleles; Animals; Binding; Celecoxib; Celecoxib - pharmacokinetics; Dialysis; Dogs; Drug development; Drug Development - methods; Drugs; Equilibrium dialysis; Female; Gene frequency; Genotyping; Liquid chromatography; Male; Mass spectrometry; Mass spectroscopy; Meloxicam; Meloxicam - pharmacokinetics; Mycophenolic acid; Mycophenolic Acid - pharmacokinetics; Nucleotides; Pharmacokinetics; Phenylurea Compounds - pharmacokinetics; Plasma; Plasma proteins; Polymorphism, Single Nucleotide; Population genetics; Protein Binding - genetics; Proteins; Pyrrolidine; Pyrrolidines - pharmacokinetics; Serum Albumin - genetics; Serum Albumin - metabolism; Single-nucleotide polymorphism; Statistical analysis; Ultracentrifugation; QC; CV; SNP; D01-4582; WSU; ACN; MS/MS; HPLC; PCR

Drug binding to plasma proteins is routinely determined during drug development. Albumin polymorphisms c.1075G>T (p.Ala359Ser) and c.1422A>T (p.Glu474Asp) were previously shown to alter plasma protein binding of a drug candidate (D01-4582, 4-[1-[3-chloro-4-[N′-(2-methylphenyl)ureido]phenylacet...