title: Evaluation of the effect of nonlinear kinetics on dosage adjustments of theophylline.
abstract: The pharmacokinetics of theophylline at two different dosage levels were studied in six adult volunteers. The subjects were allowed to reach steady-state serum concentrations of theophylline after 7 days of administration of a sustained-release oral product. There was a statistically significant decrease (p = 0.03) in the total body clearance (TBC) of theophylline at the higher dosage level. At a daily dose of 10.6 mg/kg/day, the mean TBC was 0.76 ml/min/kg, whereas at a dose of 15.7 mg/kg/day the TBC averaged 0.68 ml/min/kg. For two of the subjects, a linear increase in serum concentrations occurred with increasing doses. The remaining four subjects showed a saturation of the elimination processes at the higher dosage. The apparent maximum velocity (Vmax) calculated in these subjects averaged 2,923 mg/day. The mean Michaelis-Menten constant (Km) was 23.70 micrograms/ml. Computer-generated serum concentrations produced by a linear increase in doses predicted toxic concentrations of theophylline in two of the six subjects. The results suggest caution in employing a linear model for the individualization of theophylline therapy.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008297:Male; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood
chemical_list: D013806:Theophylline