Intrasubject Variability of Theophylline Clearance in a Morbidly Obese Patient

It is well appreciated that theophylline pharmacokinetics exhibits wide intersubject variation. Within-subject changes in clearance have been generally reported in patients with acute exacerbations of disease states such as cor pulmonale or heart failure. Apparent random changes in theophylline clearance within the same patient have recently been reported. This report describes a case of suspected changes in the clearance of theophylline in a morbidly obese patient (250 kg) over a two-month period of time. Frequent dosage adjustments were required to maintain theophylline concentrations within the range of 8.2 to 27.3 μg/ml. Possible explanations for these changes included hypoxia and medically induced starvation. Daily theophylline doses ranged from 600 to 1600 mg/d. It is concluded that in some individuals, within-subject changes in theophylline clearance can be substantial, thus requiring frequent monitoring of theophylline concentration.