Sugino H, Shimada H
Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Jpn J Pharmacol. 1997 May;74(1):29-36. doi: 10.1254/jjp.74.29.
The effects of nicardipine and nifedipine on the urinary excretion of urate were examined in rats and compared with those of diltiazem. Test drugs were administered to urethane-anesthetized oxonate-loaded rats by continuous i.v. infusion. Diltiazem (10 micrograms/rat/min), nicardipine (0.3 microgram/rat/min) and nifedipine (1.0 microgram/rat/min) caused similar reductions of systemic blood pressure and increased total renal blood flow. Diltiazem did not increase urine volume significantly. However, this drug produced obvious uricosuria, with a significant increase in the ratio of urate clearance to inulin clearance (Cua/Cin), which resulted from an increase in Cua, but not from changes in the glomerular filtration rate (GFR). Nicardipine had clear diuretic and uricosuric effects, with similar increases in Cua and GFR and, thus, no change in Cua/Cin. On the other hand, nifedipine did not have any significant effect on the renal handling of urate. These results suggest that nicardipine produces uricosuria in rats via alterations in renal hemodynamics, while the uricosuric effect of diltiazem involves the tubules, as well as alterations in renal hemodynamics.
在大鼠中研究了尼卡地平与硝苯地平对尿酸排泄的影响，并与地尔硫䓬的影响进行比较。通过持续静脉输注将受试药物给予氨基甲酸乙酯麻醉的、负荷氧嗪酸盐的大鼠。地尔硫䓬（10微克/大鼠/分钟）、尼卡地平（0.3微克/大鼠/分钟）和硝苯地平（1.0微克/大鼠/分钟）引起相似程度的全身血压降低，并增加了肾总血流量。地尔硫䓬未显著增加尿量。然而，该药产生明显的尿酸尿，尿酸清除率与菊粉清除率之比（Cua/Cin）显著增加，这是由于Cua增加，而非肾小球滤过率（GFR）改变所致。尼卡地平有明显的利尿和尿酸尿作用，Cua和GFR有相似增加，因此Cua/Cin无变化。另一方面，硝苯地平对肾脏处理尿酸没有任何显著影响。这些结果表明，尼卡地平通过改变肾脏血流动力学在大鼠中产生尿酸尿，而地尔硫䓬的尿酸尿作用涉及肾小管以及肾脏血流动力学的改变。
