A Method for Estimating Theophylline Pharmacokinetic Parameters and Its Predictability for the Serum Concentration

To estimate pharmacokinetic parameters for individualized theophylline therapy, a method available to clinical practice was studied in 2 healthy volunteers and 4 patients with bronchial asthma. At the beginning of the theophylline therapy (oral administration of aminophylline tablets 3 times daily), 2/3 of the daily dose of aminophylline was administered as a priming dose and 8 blood samples were taken for 12 hours, then residual 1/3 of the dose was administered. On the second day, a routine theophylline therapy was started, and 2 additional blood samples were taken to estimate parameters more accur ately. The ability to predict serum theophylline concentration (STC) of the method based on repetitive dosing data was compared with that based on single-dose data. There was a statistically significant correlation between observed STC, (STC) obs, and that predicted, (STC) pre, by both method, however, prediction error ((STC) pre-(STCY obs)/(STC) obs) was smaller by the method based on repetitive dosing data (ranging from-14.5 to+26.4%) than by the method based on single-dose data (from-27.9 to+48.1%). The method based on repetitive dosing data can be used in clinical practice, because approximately accurate parameters can be estimated without interrupting, a routine theophylline therapy and with a little number of blood sampling.