Influences of Cigarette-Smoke on Pharmaokinetics

研究了急性暴露于香烟烟雾和尼古丁给药对大鼠口服苯巴比妥、普里米酮和吲哚美辛药代动力学的影响。首先，建立了一种HPLC固相萃取法同时测定大鼠血浆中primidone及其活性代谢物pheny乙基丙二胺（PEMA）的方法。其次，利用上述新方法测定暴露于香烟烟雾的大鼠给药primidone时血浆中primidone及其代谢物PEMA的浓度，即使primidone和PEMA浓度降低。香烟烟雾暴露组苯巴比妥和吲哚美辛血药浓度低于非吸烟对照组。接触香烟烟雾的影响程度与香烟烟雾中尼古丁的含量成正比。另一方面，在香烟-烟雾实验中，尼古丁给药对普里米酮、苯巴比妥和吲哚美辛的药代动力学影响几乎相同。

Influences of acute exposure to smoke of cigarette smoke and nicotine administration on pharmacokinetics of orally administered phenobarbital, primidone, and indomethacin were investigated in rats.First, we developed a method of simultaneously determinig primidone and its active metabolote, phenylethylmalonamide (PEMA), in rat plasma by HPLC usiung a solid-phase extraction technique.Second, using above new method, primidone and its metabolite, PEMA,concentration in plasma were determined when primidone was adminstered to the rat exposed to cigarette smoke, i.e., resulting in lower primidone and PEMA concentration. Furthermore phenobarbital and indomethacin plasma concetrations in exposed group to cigarette smoke were lower than those in the non-smoking control group. The degree of influences of exposure to cigarette smoke was proportional to the content of nicotine in the cigarette smoke.On the other hand, effects of nicotine administration on pharmacokinetics of primidone, phenobarbital and indomethacin were almost the same result in the cigarette-smoke experiments.