Engelhardt G
Department of Biological Research, Dr. Karl Thomae GmbH, Biberach/Riss, Germany.
Arzneimittelforschung. 1996 May;46(5):509-12.
The aim of the study was to investigate the effect of acetylsalicylic acid (CAS 50-78-2, ASA), paracetamol (CAS 103-90-2) and caffeine (CAS 58-08-2) and a combination of these substances on the renal prostaglandin excretion of rats loaded with water. In addition to the effects on the renal excretion of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the effect on the electrolyte, creatinine and water excretion was measured. Even in low doses ASA led to a dose-dependent reduction in the renal PGE2 and 6-keto-PGF1 alpha excretion. In oral doses up to 200 mg/kg paracetamol did not have any effect on the renal prostanoid excretion. In the combination it did not change the effect of ASA on the prostaglandin excretion. Caffeine caused a marked dose-dependent increase in the PGE2 excretion. The effect of caffeine on the renal 6-keto-PGF1 alpha excretion was less marked. In combination with ASA, with and without the addition of paracetamol, caffeine reduced the inhibitory effect of ASA on the excretion of arachidonic acid metabolites. The values for the renal prostaglandin excretion did not show any clear correlation with the other parameters of diuresis.
本研究的目的是调查乙酰水杨酸(CAS 50-78-2,ASA)、对乙酰氨基酚(CAS 103-90-2)和咖啡因(CAS 58-08-2)以及这些物质的组合对饮水负荷大鼠肾前列腺素排泄的影响。除了对前列腺素E2(PGE2)和6-酮-前列腺素F1α(6-酮-PGF1α)肾排泄的影响外,还测量了对电解质、肌酐和水排泄的影响。即使在低剂量下,ASA也会导致肾PGE2和6-酮-PGF1α排泄呈剂量依赖性减少。口服剂量高达200 mg/kg时,对乙酰氨基酚对肾类前列腺素排泄没有任何影响。在组合中,它不会改变ASA对前列腺素排泄的影响。咖啡因导致PGE2排泄显著剂量依赖性增加。咖啡因对肾6-酮-PGF1α排泄的影响不太明显。与ASA联合使用时,无论是否添加对乙酰氨基酚,咖啡因都会降低ASA对花生四烯酸代谢产物排泄的抑制作用。肾前列腺素排泄值与其他利尿参数之间未显示出任何明显的相关性。