title: Differences in the single-oral-dose pharmacokinetics and urinary excretion of paracetamol and its conjugates between Hong Kong Chinese and Caucasian subjects.
abstract: OBJECTIVE
  The present study was conducted to determine if ethnic differences exist for single oral dose pharmacokinetics of paracetamol and its conjugates between Hong Kong Chinese and Caucasian subjects.
  
  
  METHODS
  Twenty healthy Chinese (n = 11) and Caucasian (n = 9) subjects, aged 21-44 years, 11 male and nine female, were given oral paracetamol syrup 20 mg/kg, following an overnight fast. Paracetamol and its metabolites (glucuronide, sulphate, cysteine and mercapturic acid conjugates) were measured in serial plasma samples (0.25, 0.5, 0.75, 1.0, 1.5, 2, 3,...,12, 24 h) and urine collections (0-24 h) by high-performance liquid chromatography.
  
  
  RESULTS
  In Chinese subjects, the (mean range) peak plasma concentration of paracetamol was 23.8 mug/mL (17.9-32.3) and time to attain this peak 0.66 h (0.5-0.75). This was lower (P < 0.015) at 18.7 microg/mL (14.4-22.9) and achieved later (P < 0.033) at 1.06 h (0.5-2.0) in Caucasians. In Chinese subjects, plasma levels of glucuronide were lower, sulphate higher and cysteine conjugates significantly lower than in Caucasians (P < 0.05). Chinese subjects excreted 6% more sulphate and 5% less glucuronide. They also excreted significantly less mercapturic acid conjugates (P < 0.001).
  
  
  CONCLUSIONS
  Chinese subjects show more rapid absorption of paracetamol, a tendency to produce less glucuronide but more sulphate conjugates and reduced production of cysteine and mercapturic acid conjugates. The latter may help to protect against hepatotoxicity following paracetamol overdose.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: J A J H
authors.initials: JA
authors.lastname: Critchley
authors.forename: L A H
authors.initials: LA
authors.lastname: Critchley
authors.forename: P J
authors.initials: PJ
authors.lastname: Anderson
authors.forename: B
authors.initials: B
authors.lastname: Tomlinson
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000494:pharmacology* / Q000652:urine*; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D044466:Asian People / Q000208:ethnology*; D001827:Body Height / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003545:Cysteine / Q000031:analogs & derivatives / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D020719:Glucuronides / Q000097:blood / Q000378:metabolism; D006207:Half-Life; D006723:Hong Kong / Q000208:ethnology; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D013431:Sulfates / Q000097:blood / Q000378:metabolism; D044465:White People / Q000208:ethnology*
chemical_list: D020719:Glucuronides; D013431:Sulfates; D000082:Acetaminophen; D003545:Cysteine