Reliability of theophylline clearance in determining chronic oral dosage regimens

Abstract

Predicted and approximated mean serum theophylline concentrations were compared to assess the feasibility of using theophylline clearance, calculated from the intravenous steady-state serum theophylline concentration, to determine appropriate oral dosage requirements. Ten patients with reversible airway disease (age 7 to 64 years) received theophylline (as Aminophylline USP) by constant i.v. infusion. Theophylline clearance was calculated for each patient from steady-state serum theophylline concentrations determined from blood samples obtained after a least 48 hours of constant theophylline infusion. Aminophylline USP tablets were then adminstered orally. Blood levels measured at peak and trough times following oral theophylline administration were used to calculate an approximate mean serum theophylline concentration. The relationship between predicted and approximated mean serum theophylline concentrations was calculated and analyzed by orthogonal least square regression line. Serum theophylline concentrations ranged from 5.1 μg/ml to 20.1 μg/ml, and clearances ranged from 0.03 liter/kg/hr to 0.09 liter/kg/hr. During oral therapy, the maximum concentration ranged from 10.4 μg/ml to 23.8 μg/ml, while the minimum ranged from 6.5 μg/ml to 15.2 μg/ml. The difference between predicted and approximated mean serum concentrations was within ±1.6 μg/ml in all cases. The study indicates that the theophylline clearance calculated from i.v. infusion data can be used to determine appropriate oral dosage requirements.