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

ABSTRACT

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.