Zafar N U, Niazi S, Jung D
J Pharm Pharmacol. 1987 Feb;39(2):144-7. doi: 10.1111/j.2042-7158.1987.tb06965.x.
The effect of acute (96 h) water deprivation on the disposition of paracetamol (acetaminophen) has been examined in male Sprague-Dawley rats. Plasma and urinary concentrations of the drug and its two major metabolites, the glucuronide and sulphate, were determined by a sensitive and specific high performance liquid chromatographic assay. Following an intravenous dose of 100 mg kg-1 of paracetamol, no significant changes were found in the elimination rate constant (k), the mean residence time (MRT), total plasma clearance (Cl) and the apparent volume of distribution at steady-state (Vss). However, rats deprived of water for 96 h excreted a larger percentage of the administered dose as the glucuronide conjugate (15.3 vs 7.9%) and a smaller percentage as unchanged paracetamol (7.3 vs 20.7%) in the urine. In addition, there was a significant two-fold increase in the partial metabolic clearance to paracetamol glucuronide. Water deprivation also led to a significant reduction in the renal clearance of paracetamol accompanied by an increase in the renal clearance of the glucuronide.
在雄性斯普拉格-道利大鼠中研究了急性（96小时）缺水对扑热息痛（对乙酰氨基酚）处置的影响。通过灵敏且特异的高效液相色谱分析法测定了药物及其两种主要代谢物（葡萄糖醛酸苷和硫酸盐）的血浆和尿液浓度。静脉注射100mg/kg扑热息痛后，消除速率常数（k）、平均驻留时间（MRT）、总血浆清除率（Cl）和稳态时的表观分布容积（Vss）均未发现显著变化。然而，缺水96小时的大鼠尿液中以葡萄糖醛酸苷结合物形式排泄的给药剂量百分比更高（15.3%对7.9%），而以未变化的扑热息痛形式排泄的百分比更低（7.3%对20.7%）。此外，扑热息痛葡萄糖醛酸苷的部分代谢清除率显著增加了两倍。缺水还导致扑热息痛的肾清除率显著降低，同时葡萄糖醛酸苷的肾清除率增加。
