title: Evaluation of the effect of variability in the volume of distribution of theophylline on the predictability of the iterative and the Chiou methods using computer simulations.
abstract: The effect of variations in the volume of distribution on the precision of the ability of two methods--the Chiou and the iterative--to predict the total body clearance (TBC) of theophylline was evaluated utilizing computer simulations. Pharmacokinetic data [volume of distributions (V), elimination constants (k)] measured in a group of 55 adult bronchitic patients were utilized to conduct the simulations. An average V of 0.45 L/kg was utilized to calculate TBC with the Chiou and the iterative methods. Separate simulations were conducted utilizing initial (C1) serum concentrations of 2 and 10 micrograms/ml. At the C1 = 2 micrograms/ml condition, the iterative method was statistically significantly more precise (mean squared prediction error, 379.5 vs. 508.5). There were no differences when the initial serum concentration was 10 micrograms/ml under the simulated conditions. At the lower initial condition (C1 = 2) the mean prediction error was 62.3 and 54.9% for the Chiou and the iterative methods, respectively, and it ranged from 0 to 477%. It is recommended that caution be utilized when theophylline doses are individualized using these methods.
mesh_terms: D000328:Adult; D006801:Humans; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008722:Methods; D008838:Microcomputers; D008954:Models, Biological; D013806:Theophylline / Q000378:metabolism*
chemical_list: D013806:Theophylline