Fleck C, Nguyen T T, Bräunlich H
Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, G.D.R.
Exp Pathol. 1988;35(2):115-27.
The pharmacokinetics of a series of 6-sulfonamides, with gradually increasing molecular weights, were studied in anaesthetized rats after intravenous bolus injection. Immature (20-day-old) and adult (55-day-old) rats were compared. In both age groups renal excretion of all sulfonamides tested here dominates (about 5- to 10-fold). In 20-day-old rats renal and hepatic excretions are immature and reach about 50% (liver) or 30% (kidney) of adult values. Relation between renal and hepatic excretion of sulfonamides is strongly correlated to the lipophilicity of these substances. Hepatic excretion of sulfonamides seems to be correlated to their pKa-values. Concerning their excretion via urine it is necessary to correlate different steps of renal transport to physico-chemical properties in detail. A general correlation between renal excretion of sulfonamides and their chemical structure obviously does not exist. After bile duct ligation 24 h before clearance experiments no compensatory increase of renal sulfonamide excretion occurs. 24 h following bilateral nephrectomy hepatic excretion of sulfonamides is significantly enhanced; however, this phenomenon is related to physico-chemical properties of the sulfonamides. Age differences in compensation of one elimination pathway do not exist.
在麻醉大鼠静脉推注后,研究了一系列分子量逐渐增加的6 - 磺胺类药物的药代动力学。比较了未成熟(20日龄)和成年(55日龄)大鼠。在这两个年龄组中,此处测试的所有磺胺类药物的肾排泄占主导(约为5至10倍)。在20日龄大鼠中,肾和肝排泄不成熟,分别达到成年值的约50%(肝脏)或30%(肾脏)。磺胺类药物的肾排泄与肝排泄之间的关系与这些物质的亲脂性密切相关。磺胺类药物的肝排泄似乎与其pKa值相关。关于它们通过尿液的排泄,有必要详细地将肾转运的不同步骤与物理化学性质相关联。磺胺类药物的肾排泄与其化学结构之间显然不存在普遍的相关性。在清除实验前24小时进行胆管结扎后,肾磺胺排泄没有出现代偿性增加。双侧肾切除术后24小时,磺胺类药物的肝排泄显著增强;然而,这种现象与磺胺类药物的物理化学性质有关。不存在一种消除途径代偿方面的年龄差异。