Dose-dependent theophylline elimination in an adult

A 69-year-old male patient with chronic obstructive pulmonary disease exhibited dose-dependent theophylline elimination. Steady-state serum theophylline concentrations, obtained at five different aminophylline infusion rates, ranged from 2.0 mg/L at an infusion rate of 36 mg/h to 10.1 mg/L at 76 mg/h. These serum concentrations were nonlinearly related to dose, with a Vmax of 89.04 mg/h and Km of 3.96 mg/L (r = 0.983, p less than 0.005). Theophylline clearance fell from a high of 348 ml/kg/h to 145 ml/kg/h as the infusion rate was increased. Although theophylline elimination kinetics in adults are generally assumed to be linear, clinicians should be alert to the possibility of nonlinear theophylline elimination, as has been observed commonly in children.