Differences in the single-oral-dose pharmacokinetics and urinary excretion of paracetamol and its conjugates between Hong Kong Chinese and Caucasian subjects.

BACKGROUND AND OBJECTIVES: 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...

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Publicado en:Journal of Clinical Pharmacy & Therapeutics Vol. 30; no. 2; pp. 179 - 185
Autores principales: Critchley JAJ, Critchley LAH, Anderson PJ, Tomlinson B
Formato: research tables/charts Journal Article
Publicado: Wiley-Blackwell Apr2005
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Apr2005
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        atl: Differences in the single-oral-dose pharmacokinetics and urinary excretion of paracetamol and its conjugates between Hong Kong Chinese and Caucasian subjects.
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        au:
          Critchley JAJ
          Critchley LAH
          Anderson PJ
          Tomlinson B
        affil: Division of Clinical Pharmacology, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
      sug:
        subj:
          Acetaminophen Pharmacokinetics
          Asians
          Drugs Metabolism
          White Persons
          Acetaminophen Urine
          Administration, Oral
          Adult
          Data Analysis, Statistical
          Descriptive Statistics
          Ethnic Groups
          Female
          Hong Kong
          Male
          Prospective Studies
          Human
          Adult: 19-44 years
          Female
          Male
      ab: BACKGROUND AND OBJECTIVES: 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). DISCUSSION AND CONCLUSION: 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.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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