THE ROLE OF SULFATE CONJUGATION IN THE METABOLISM AND DISPOSITION OF ORAL AND INTRAVENOUS PARACETAMOL IN MAN
THE ROLE OF SULFATE CONJUGATION IN THE METABOLISM AND DISPOSITION OF ORAL AND INTRAVENOUS PARACETAMOL IN MAN
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DOI：
10.1111/j.1365-2125.1984.tb02495.x
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发表时间：
1984-01-01
影响因子：
3.4
通讯作者：
PRESCOTT, LF
中科院分区：
文献类型：
--
作者：
CLEMENTS, JA;CRITCHLEY, JAJH;PRESCOTT, LF
对乙酰氨基酚的剂量(5 mg/kg和20 mg/kg)和给药途径(静脉注射)的影响。对5名健康受试者尿液中对乙酰氨基酚及其葡聚糖、硫酸盐、半胱氨酸和硫代尿酸结合物的排泄进行了研究。在两个剂量水平下，未改变的扑热息痛及其结合物的尿排出分数与给药途径无关，表明胃肠道不是扑热息痛代谢的重要部位。硫酸盐结合物的排泄百分率在5 mg/kg后显著高于20 mg/kg后(分别为37.7%和33.3%)，这与硫酸盐结合的饱和度相一致。对于硫酸盐或葡萄糖醛酸偶联物，没有发现扑热息痛剂量对血浆浓度-时间曲线(AUC)下的面积(经剂量校正)有显著影响。5 mg/kg剂量后，扑热息痛的血浆总清除量和硫酸盐结合物的肾清除量显著高于20 mg/kg剂量组(33.1±-)。42ml/min和295。+-。48ml/min；273.+-。74ml/min和205.+-。分别为46ml/min)。扑热息痛的口服系统利用度为80%，且与剂量无关。
The effects of paracetamol dose (5 and 20 mg/kg) and route of administration (i.v. and oral) on the urinary excretion of paracetamol and its glucoronide, sulfate, cysteine and mercapturic acid conjugates were studied in 5 healthy subjects. The fractional urinary excretion of unchanged paracetamol and its conjugates was independent of the route of administration at both dose levels, suggesting that the gastrointestinal tract is not an important site for paracetamol metabolism. The percentage of the dose excreted as the sulfate conjugate was significantly higher after 5 than after 20 mg/kg (37.7% and 33.3%, respectively) and this is consistent with saturation of sulfate conjugation. No significant effect of paracetamol dose upon the area under the plasma concentration-time curve (AUC), corrected for dose, was found for the sulfate or glucuronide conjugates. The total plasma clearance of paracetamol and the renal clearance of the sulfate conjugate were significantly higher after the 5 than the 20 mg/kg dose (331 .+-. 42 ml/min and 295 .+-. 48 ml/min; 273 .+-. 74 ml/min and 205 .+-. 46 ml/min, respectively). The oral systemic availability of paracetamol was 80% and independent of dose.