Príborský J, Takayama K, Nagai T
Glaxo Wellcome s.r.o., Prague, Czech Republic.
Acta Univ Palacki Olomuc Fac Med. 1998;141:35-8.
The influence of uraemia on percutaneous absorption of three model drugs (diclofenac, ibuprofen and indomethacin) which are eliminated entirely via nonrenal route was investigated in the rats. Following day after bilateral nephrectomy (BUN levels were between 30-50 mmol/l), gel ointment containing drugs under test was applied on the abdominal site of the skin. Comparing with the sham operated controls the percutaneous absorption significantly decreased in all three challenged substances. Influence on percutaneous absorption of indomethacin was investigated more in depth as this compound can serve as a model for other nonsteroid anti-inflammatory drugs. The 50 mmol/l concentration of urea (equal to uraemia) added to the gel ointment did not influence percutaneous absorption while 10% concentration of urea decreased percutaneous absorption of indomethacin approximately 5 times. Solubility of indomethacin increased in the presence of 10% urea in the gel more than two times. Elimination ratios Q0 were estimated to find if there is any effect on pharmacokinetics linked directly to the renal elimination. None of such changes were observed.
在大鼠中研究了尿毒症对三种完全通过非肾途径消除的模型药物（双氯芬酸、布洛芬和吲哚美辛）经皮吸收的影响。双侧肾切除术后一天（血尿素氮水平在30 - 50 mmol/l之间），将含受试药物的凝胶软膏涂抹于腹部皮肤部位。与假手术对照组相比，所有三种受试物质的经皮吸收均显著降低。由于吲哚美辛可作为其他非甾体抗炎药的模型，因此对其经皮吸收的影响进行了更深入的研究。向凝胶软膏中添加50 mmol/l浓度的尿素（等同于尿毒症）对经皮吸收没有影响，而10%浓度的尿素使吲哚美辛的经皮吸收降低了约5倍。在凝胶中存在10%尿素的情况下，吲哚美辛的溶解度增加了两倍多。估计消除率Q0以确定是否对直接与肾排泄相关的药代动力学有任何影响。未观察到此类变化。
