title: Protein-Derived Acetaminophen-Cysteine Can Be Detected After Repeated Supratherapeutic Ingestion of Acetaminophen in the Absence of Hepatotoxicity.
abstract: Generation of protein-derived acetaminophen-cysteine (APAP-CYS) is reported after ingestion of large and therapeutic dosages of acetaminophen in healthy and in liver-damaged patients. The incidence of protein-derived APAP-CYS adducts in repeated supratherapeutic dosages of APAP is not known.
  
  
  METHODS
  for 12 months, a standardized and comprehensive questionnaire was used to interview every consecutive patient at a pain management clinic. Patients found to ingest more than 4 g of APAP per day for a minimum of 14 consecutive days at the time of the encounter were invited to have blood drawn for hepatic transaminases and APAP-CYS adduct levels. Twelve subjects out of 990 interviewees met inclusion criteria. Ten of the 12 had measurable protein-derived APAP-CYS, none had evidence of liver injury. Patients that ingest repeated supratherapeutic amounts of APAP over several weeks may generate APAP-CYS protein adducts in the absence of hepatic injury.
authors.affiliation: Albert Einstein Medical Center, Philadelphia, PA, USA, geraldomalley@gmail.com.
authors.forename: G F
authors.initials: GF
authors.lastname: O'Malley
authors.forename: F
authors.initials: F
authors.lastname: Mizrahi
authors.forename: P
authors.initials: P
authors.lastname: Giraldo
authors.forename: R N
authors.initials: RN
authors.lastname: O'Malley
authors.forename: D
authors.initials: D
authors.lastname: Rollins
authors.forename: D
authors.initials: D
authors.lastname: Wilkins
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood*; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000175:diagnosis / Q000188:drug therapy*; D018710:Pain Clinics; D011485:Protein Binding; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D000082:Acetaminophen; C069744:acetaminophen cysteine; D000637:Transaminases; D003545:Cysteine