Fujimura A, Kajiyama H, Ohashi K, Ebihara A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Jpn J Pharmacol. 1991 May;56(1):43-51. doi: 10.1254/jjp.56.43.
We have previously demonstrated a time-dependent variability in the diuretic effects of S-8666, a new loop diuretic with uricosuric activity, in young rats. The present study was undertaken to determine whether such a daily variation in the effects of the agent exists in aged rats. S-8666 (30 and 90 mg/kg) was orally given at 12:00 a.m. (day trial) or at 12:00 p.m. (night trial) in young (10-11 week old) and aged (23-24 month old) Wistar rats. Urine was collected for 8 hours after the agent; and urinary excretions of sodium, S-8666 and its active metabolite S-8680 were determined. Urinary excretions of volume and sodium following S-8666 at 12:00 a.m. were greater than those at 12:00 p.m. in the young and aged animals. Urinary excretions of S-8666 and S-8680 were also greater in the day trial compared to those in the night trial in both groups of rats. In the day and night trials, there were significant correlations between urinary S-8666 + S-8680 and the diuretic effects in both groups of rats. These findings indicate that the diuretic effects of S-8666 also vary with its time of dosing in aged rats. The time-dependent variations in urinary S-8666 and S-8680 might be involved in this phenomenon.
我们之前已经证明，新型袢利尿剂S - 8666具有促尿酸排泄活性，其利尿作用在幼龄大鼠中存在时间依赖性变化。本研究旨在确定该药物在老年大鼠中是否也存在这种每日效应变化。在年轻（10 - 11周龄）和老年（23 - 24月龄）Wistar大鼠中，于上午12:00（日间试验）或下午12:00（夜间试验）口服给予S - 8666（30和90 mg/kg）。给药后收集8小时尿液；并测定尿液中钠、S - 8666及其活性代谢物S - 8680的排泄量。在年轻和老年动物中，上午12:00给予S - 8666后，尿液体积和钠的排泄量均大于下午12:00给予时。在两组大鼠中，日间试验中S - 8666和S - 8680的尿液排泄量也高于夜间试验。在日间和夜间试验中，两组大鼠尿液中S - 8666 + S - 8680与利尿作用之间均存在显著相关性。这些发现表明，S - 8666在老年大鼠中的利尿作用也随给药时间而变化。尿液中S - 8666和S - 8680的时间依赖性变化可能与这一现象有关。
