Influences of Cigarette-Smoke on Pharmaokinetics

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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.