title: Biomarker discovery for drug-induced phospholipidosis: phenylacetylglycine to hippuric acid ratio in urine and plasma as potential markers.
abstract: BACKGROUND
  Drug-induced phospholipidosis is one of the significant concerns in drug development, especially in safety assessment and noninvasive diagnostic tool is highly desirable.
  
  
  OBJECTIVE
  The objective of this study is to explored novel biomarkers for phospholipidosis using a metabolomic approach.
  
  
  METHODS
  NMR spectrometry and LC/MS/MS analyses were applied to urine and plasma of rats administrated cationic amphiphilic drugs.
  
  
  RESULTS
  The phenylacetylglycine to hippuric acid ratio in plasma was increased in time and dose-dependent manners; and it was well correlated with histopathological observation.
  
  
  CONCLUSIONS
  The plasma phenylacetylglycine to hippuric acid ratio is a potential marker in monitoring drug-induced phospholipidosis.
authors: a Integrated Technology Research Laboratories , Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors: Hidenori
authors: H
authors: Kamiguchi
authors: b Process Chemistry, Pharmaceutical Science , Takeda Pharmaceutical Company Limited , Osaka , Japan.
authors: Mika
authors: M
authors: Murabayashi
authors: a Integrated Technology Research Laboratories , Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors: Ikuo
authors: I
authors: Mori
authors: c PS Administration Department, Pharmaceutical Science , Takeda Pharmaceutical Company Limited , Osaka , Japan.
authors: Akira
authors: A
authors: Horinouchi
authors: d Department of Pharmaceutics, Faculty of Pharmaceutical Sciences , Okayama University , Okayama , Japan.
authors: Kazutaka
authors: K
authors: Higaki
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis* / Q000097:blood / Q000652:urine; D016903:Drug Monitoring / Q000379:methods; D005998:Glycine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000652:urine; D006626:Hippurates / Q000032:analysis* / Q000097:blood / Q000652:urine; D008064:Lipidoses / Q000139:chemically induced / Q000175:diagnosis*; D055432:Metabolomics / Q000379:methods; D010743:Phospholipids; D051381:Rats
chemical_list: D015415:Biomarkers; D006626:Hippurates; D010743:Phospholipids; C022050:phenylacetylglycine; C030514:hippuric acid; D005998:Glycine
keywords: Phenylacetylglycine; drug-induced phospholipidosis; hippuric acid; phenylalanine metabolism