Effects of smoking, sex and age on theophylline pharmacokinetics in Thais

Abstract

The effects of cigarette smoking, sex and age on theophylline pharmacokinetics were examined in 40 healthy Thai volunteers. They were devided into 4 groups (n = 10): nonsmoking males (23-38 yrs), nonsmoking females (22-34 yrs), smoking males (21-33 yrs) and children (7-12 yrs). An oral dose of 2.4 mg / kg body weight of theophylline syrup was given to each subject. Plasma theophylline concentrations were measured by high-performance liquid chromatographic method. The plasma concentration-time data were fitted to a one-compartment open model using the PCNONLIN, a nonlinear regression computer program. In nonsmoking males, nonsmoking females, smoking males and children. the apparent volume of distribution (V) were 0.484 L/kg. 0.380 L/kg. 0.457 L / kg 0.417 L / kg.; the elimination rate constant (K) were 0.0787 hr-1.0.0790 hr-1 0.1020 hr-1. 0.1327 hr-1; the total body clearance (Cl) were 0.038 L/kg/hr. 0.030 L/kg/hr. 0.047 L/kg/hr, 0.056 L/kg/hr and the elimination half-life (t1/2 were 8.81 hr.8.77 hr. 6.80 hr. 5.22 hr, respectively. The results demonstrated significant effects of smoking sex and age on theophylline pharmacokinetic parameters. Mean V in females was smaller than in males (p <0.05). Mean Cl in males was higher than in females (p <0.05). whereas no difference in k was observed. The elimination rate constant was observed to be statistically significantly increased in cigarette smoking subjects (p <0.05). Mean Cl in smokers also was higher than nonsmokers but the difference was not significant. Children eliminated theophylline faster than adults as reflected by both significantly increased k and cl (p <0.05).