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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.

INFLUENCES OF LONG-TERM CIGARETTE SMOKE EXPOSURE ON PHARMACOKINETICS OF THEOPHYLLINE, AND ON LIVER MICROSOMAL ENZYMES IN RATS