Fleck C, Kabath P, Linstedt A, Linstedt U, Scharke U, Bräunlich H
Friedrich Schiller University, Institute of Pharmacology and Toxicology, Jena, Germany.
Exp Pathol. 1991;43(1-2):75-87. doi: 10.1016/s0232-1513(11)80150-7.
Ioglycamic acid (IGA) is effectively eliminated in young and adult rats via urine and bile. After administration of low doses hepatic excretion dominates whereas following high supply renal elimination surpasses biliary excretion. Hepatic transport of IGA is active, indicated by the occurrence of a transport maximum in vivo and by a distinct accumulation of this drug within liver slices in vitro. Renal removal of IGA is preferentially caused by glomerular filtration. A tubular reabsorption obviously does not occur because forced diuresis (mannitol, furosemide) does not increase renal excretion of this substance. As calculated from our clearance data and as a result of accumulation experiments in vitro on renal cortical slices the active tubular secretion of this organic anion can be excluded. In principle there are no qualitative changes in IGA elimination between the 20th and 55th day of life, but active hepatic transport of the drug is significantly lower in young, immature rats. After bile duct ligation, renal excretion of IGA increases distinctly in both age groups, whereas in adult rats bilateral nephrectomy (NX) is followed by a significant decrease in its hepatic excretion in dependence on time after kidney removal. In young rats NX is without consequences on hepatic excretion of IGA. It is possible to stimulate renal and/or hepatic excretion of IGA by repeated administration of T3, dexamethasone, or phenobarbital. The effect of stimulation is different in kidney and liver and depends on age, too.
碘甘氨酸(IGA)在幼年和成年大鼠体内可通过尿液和胆汁有效清除。低剂量给药后,肝脏排泄占主导,而高剂量给药后,肾脏清除超过胆汁排泄。IGA的肝脏转运是活跃的,这在体内表现为转运最大值的出现,在体外肝脏切片中表现为该药物的明显蓄积。IGA的肾脏清除主要由肾小球滤过引起。显然不存在肾小管重吸收,因为强制利尿(甘露醇、呋塞米)并不会增加该物质的肾脏排泄。根据我们的清除率数据计算,以及体外对肾皮质切片进行的蓄积实验结果,可排除该有机阴离子的活跃肾小管分泌。原则上,在出生后第20天至第55天之间,IGA清除没有质的变化,但在幼年未成熟大鼠中,该药物的活跃肝脏转运明显较低。胆管结扎后,两个年龄组的IGA肾脏排泄均明显增加,而在成年大鼠中,双侧肾切除(NX)后,其肝脏排泄会根据肾切除后的时间显著减少。在幼年大鼠中,NX对IGA的肝脏排泄没有影响。通过重复给予T3、地塞米松或苯巴比妥,可以刺激IGA的肾脏和/或肝脏排泄。刺激作用在肾脏和肝脏中有所不同,并且也取决于年龄。