Yoshida T, Gomita Y, Oishi R
Department of Pharmacology, Okayama University Medical School, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1991 Oct;344(4):500-4. doi: 10.1007/BF00172592.
The effect of cigarette smoke exposure on the pharmacokinetics of indomethacin administered orally, intravenously or intrarectally was investigated in rats. When cigarette smoke exposure was performed for 10 min using a Hamburg II smoking machine immediately after the oral administration of indomethacin (5 mg/kg), the plasma indomethacin concentration was significantly lowered during the first 2 h after administration. However, there was no significant difference in plasma indomethacin concentration between the cigarette smoke-exposed and nonexposed control rats thereafter. Cigarette smoke exposure caused a significant decrease in the area under the concentration-time curve from 0 to 4 h (AUC0-4) and a prolongation of the time to reach the maximum concentration (tmax). The plasma level of O-desmethyl-indomethacin (a major metabolite) was not significantly changed by cigarette smoke. When indomethacin (5 mg/kg) was administered to rats intravenously or intrarectally, cigarette smoke exposure did not have any influence on the pharmacokinetics of indomethacin or 0-desmethyl-indomethacin. The pharmacokinetic effect of cigarette smoke on orally administered indomethacin was mimicked by the subcutaneous injection of nicotine at 0.3 mg/kg but not at 0.1 mg/kg. These results suggest that acute exposure to cigarette smoke decreases the plasma concentration of indomethacin when it is administered orally but not intrarectally or intravenously.
研究了香烟烟雾暴露对大鼠口服、静脉注射或直肠内给予吲哚美辛的药代动力学的影响。在口服吲哚美辛（5mg/kg）后立即使用汉堡II型吸烟机进行10分钟的香烟烟雾暴露，给药后最初2小时内血浆吲哚美辛浓度显著降低。然而，此后暴露于香烟烟雾的大鼠与未暴露的对照大鼠之间血浆吲哚美辛浓度没有显著差异。香烟烟雾暴露导致0至4小时浓度-时间曲线下面积（AUC0-4）显著降低，达到最大浓度的时间（tmax）延长。O-去甲基吲哚美辛（一种主要代谢物）的血浆水平未因香烟烟雾而显著改变。当给大鼠静脉注射或直肠内给予吲哚美辛（5mg/kg）时，香烟烟雾暴露对吲哚美辛或O-去甲基吲哚美辛的药代动力学没有任何影响。香烟烟雾对口服吲哚美辛的药代动力学影响可通过皮下注射0.3mg/kg尼古丁模拟，但0.1mg/kg则不能。这些结果表明，急性暴露于香烟烟雾会降低口服吲哚美辛时的血浆浓度，但对直肠内或静脉注射给药则无此影响。
