Effect of Smoking on Theophylline Pharmacokinetics in Normal Korean Volunteers

In order to evaluate the effect of cigarette smoking on the pharmacokinetics of theophylline in Koreans, doses of 4.5 to 5.0 mg/kg of theophylline, as injectable aminophylline, were administered to 12 normal young volunteers (male, 22 to 35 yrs;mean, 26 yrs) through intravenous infusion over 30 minutes, and pharmacokinetics of theophylline were tested. Among subjects, six were nonsmokers and the other were smokers (range 1 to 2 packs/day). Also the correlations between plasma and saliva theophylline concentrations were investigated by determining the concentrations of theophylline in saliva simultaneously at each plasma sampling time. The total body clearances of theophylline in smokers (Mean${\pm}$SD, 0.0578${\pm}$0.0092 L/hr/kg)were appreciably higher than thoxe of nonsmokers (Mean${\pm}$SD, 0.0359${\pm}$0.0063 L/hr/kg), and the half-lives of theophylline in smokers averaged 5.36${\pm}$1.22hr, and significantly shorter than those of nonsmokers which averaged 9.14${\pm}$1.73hrs(p<0.005). But the apparent volumes of distribution of theophylline did not show any significant difference between smokers (Mean${\pm}$SD,0.44 ${\pm}$0.05L/kg) and nonsmokers (Mean${\pm}$SD, 0.46${\pm}$0.05L/kg). The average concentration ratios in saliva and plasma were 0.61 in smokers and 0.56 in nonsmokers after 2 hrs following drug administrations, and the smoker group had a slightly higher value of ratio(S/P) than the nonsmoker group (p<0.05). The correlations between saliva and plasma theophylline concentration in smokers were r=0.852(p<0.0005) within 2 hr and r=0.985(p<0.0005) after 2 hrs and also those of nonsmokers were r=0.729(p<0.0005) within 2 hrs and r=0.957(p<0.0005) after 2 hrs starting the infusion. From the results, it was found that smoking cigarettes had significantly increased the clearance of theophylline and that the relationships between saliva and plasma theophylline concentrations in all subjects were better after 2 hrs than within 2 hrs starting the infusion of aminophlline.