Evaluation of theophylline population pharmacokinetics in adult hospitalized patients using NONMEM analysis

The population pharmacokinetics of theophylline was evaluated using 374 theophylline serum concentration measurements from 72 hospitalized patients through NONMEM analysis. An one-compartment open pharmacokinetic model with first-order absorption and first-order elimination was used. The effects of a variety of factors on Cl and Vd were investigated. Hypothesis testing to evaluated potentially significant factors produced a final regression model. There were about 1.25% per year decrease in Cl at the age of 18-77. Cl was reduced by 26.8% for patients with long history of theophylline administration and multiple dosings, and reduced by 33.9% in OLD patients. Sex, body weight, and coadministration of acetylspiramycin had no significant effects on Cl. Vd was proportional to body weight. The final regression model allowed a priori estimate of the theophylline pharmacokinetic parameters in the patients. These results may be helpful to a rational individualized theophylline dosage regimen.