Eto K, Gomita Y, Furuno K, Mimaki Y, Okazaki M, Araki Y
Department of Hospital Pharmacy, Okayama University Medical School, Japan.
Drug Metabol Drug Interact. 1992;10(4):265-77. doi: 10.1515/dmdi.1992.10.4.265.
The influences of long-term cigarette smoke exposure on pharmacokinetics of oral theophylline (20 mg/kg), and on liver microsomal enzymes which metabolize drugs were studied in rats. Animals were exposed to cigarette smoke for 20 min each in the morning and evening every day for 26 days in the pharmacokinetic study, and 27 days for the enzyme assays. Theophylline was administered 13 h after the last exposure to smoke, and plasma concentrations were measured using HPLC. Plasma concentrations of theophylline during the absorption phase and 6 h after oral administration were lower in the long-term cigarette smoke-exposed group than in the control group. In the smoke-exposed group, the AUC and Ka were lower, and the Ke was slightly higher than in the control group. Liver weight and the ratio of liver weight to body weight were lower in the smoke-exposed group, and cytochrome b5 content and NADPH-cytochrome P-450 reductase activity were higher, but cytochrome P-450 content did not differ from the control group. These results indicate that long-term exposure to cigarette smoke suppresses theophylline absorption from the gastrointestinal tract, accelerates its elimination, and affects liver microsomal enzymes which metabolize drugs.
研究了长期接触香烟烟雾对大鼠口服氨茶碱（20毫克/千克）药代动力学以及对代谢药物的肝脏微粒体酶的影响。在药代动力学研究中，动物每天早晚各暴露于香烟烟雾中20分钟，持续26天；在酶分析实验中持续27天。在最后一次暴露于烟雾后13小时给予氨茶碱，并使用高效液相色谱法测量血浆浓度。长期接触香烟烟雾的组在吸收阶段和口服给药后6小时的氨茶碱血浆浓度低于对照组。在烟雾暴露组中，曲线下面积（AUC）和吸收速率常数（Ka）较低，消除速率常数（Ke）略高于对照组。烟雾暴露组的肝脏重量以及肝脏重量与体重的比值较低，细胞色素b5含量和还原型辅酶Ⅱ-细胞色素P-450还原酶活性较高，但细胞色素P-450含量与对照组无差异。这些结果表明，长期接触香烟烟雾会抑制氨茶碱从胃肠道的吸收，加速其消除，并影响代谢药物的肝脏微粒体酶。
