title: The impact of therapeutic doses of paracetamol on serum total antioxidant capacity.
abstract: BACKGROUND
  A link between regular paracetamol intake and asthma in adults has recently been postulated. Detoxification of paracetamol may deplete stores of glutathione, which is one of the major antioxidants present in the lung. A reduced source of glutathione in the lung may lead to increased oxidative damage to the epithelium and hence increased frequency and severity of asthma attacks in susceptible individuals.
  
  
  OBJECTIVE
  This study aimed to determine whether regular intake of maximum therapeutic doses of paracetamol reduced serum antioxidant capacity in healthy volunteers.
  
  
  METHODS
  Fifteen young healthy volunteers (nine men, six women, mean age 21.3 years, range 19-32) took maximum therapeutic doses of paracetamol (1 g four times a day) for 14 days. On days 0 and 14 blood samples were taken at baseline and hourly for a period of 4 h following ingestion of 1 g paracetamol. Single venous blood samples were collected 1 h after ingestion of 1 g paracetamol on days 4, 7 and 10. Blood samples were analysed for serum paracetamol concentration and total antioxidant capacity.
  
  
  RESULTS
  Mean total antioxidant capacity was significantly reduced over the 3-h post-dosing on both days 0 and 14 (P < 0.01). The results from days 4, 7 and 10 showed a trend towards reduced antioxidant activity over time. On day 14 values were consistently lower compared with the corresponding times on day 0 (P < 0.01 at 0, 1, 3 and 4 h, P < 0.05 at 2 h).
  
  
  CONCLUSIONS
  Chronic ingestion of maximum therapeutic doses of paracetamol depletes serum antioxidant capacity in healthy volunteers in as few as 14 days, possibly by a reduction in glutathione. This may have implications for analgesic use in asthmatic individuals. Further studies are now required to assess the impact of paracetamol on antioxidant defences in the lung.
authors.affiliation: Department of Clinical Pharmacology, Division of Medical Sciences and Wolfson Applied Technology Laboratory, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Nuttall
authors.forename: J N
authors.initials: JN
authors.lastname: Khan
authors.forename: G H
authors.initials: GH
authors.lastname: Thorpe
authors.forename: N
authors.initials: N
authors.lastname: Langford
authors.forename: M J
authors.initials: MJ
authors.lastname: Kendall
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D044967:Serum; D013997:Time Factors
chemical_list: D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D000082:Acetaminophen