Differences in the single-oral-dose pharmacokinetics and urinary excretion of paracetamol and its conjugates between Hong Kong Chinese and Caucasian subjects
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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DOI：
10.1111/j.1365-2710.2004.00626.x
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发表时间：
2005-04-01
影响因子：
2
通讯作者：
Tomlinson, B
中科院分区：
文献类型：
--
作者：
Critchley, JAJH;Critchley, LAH;Tomlinson, B
背景和目标：本研究旨在确定香港中国受试者和白人受试者之间对乙酰氨基酚及其结合物的单次口服药代动力学是否存在种族差异。方法：20名健康中国受试者（n = 11）和白人（n = 9）受试者，年龄21-44岁，其中11名男性和9名女性，禁食过夜后口服对乙酰氨基酚糖浆20 mg/kg。在系列血浆样本（0.25、0.5、0.75、1.0、1.5、2、3、.、结果：在中国受试者中，对乙酰氨基酚的血浆峰浓度（平均范围）为23.8 μ g/mL（17.9-32.3），达到此峰的时间为0.66 h（0.5-0.75）。在高加索人中，18.7 μ g/mL（14.4-22.9）时较低（P < 0.015），1.06 h（0.5-2.0）时较晚（P < 0.033）。中国受试者的血浆葡萄糖醛酸苷水平低于白人，硫酸盐水平高于白人，半胱氨酸结合物水平显著低于白人（P < 0.05）。中国受试者的硫酸盐排泄量增加6%，葡糖苷酸排泄量减少5%。他们也排泄出明显更少的巯基尿酸共轭物（P < 0.001）。讨论和结论：中国受试者对扑热息痛的吸收更快，产生更少的葡萄糖醛酸苷，但更多的硫酸盐共轭物，减少半胱氨酸和巯基尿酸共轭物的产生。后者可能有助于防止扑热息痛过量后的肝毒性。
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 mu g/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 mu g/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.