OBJECTIVE To investigate the effect of parenteral nutrition on theophylline disposition in malnourished patients. METHODS Before-after trial. METHODS Tertiary care center. METHODS Ten patients with historic, anthropometric, and laboratory evidence of malnutrition. METHODS Patients received two 5-mg/kg intravenous infusions of theophylline separated by at least 48 hours of glucose-based parenteral nutrition providing the entire estimated nutritional requirements. METHODS Following each theophylline administration, serum theophylline samples were collected over a 24-hour period for delineation of maximum plasma concentrations, volume of distribution, elimination rate constant, clearance, and area under the curve. RESULTS Peak plasma theophylline concentrations were significantly lower prior to feeding (5.3 mumol/L, 95 percent confidence interval [CI] 0.78-10.0 mumol/L, p = 0.028). Volume of distribution decreased after parenteral feeding (0.08 L/kg, 95 percent CI 0.006-0.15 L/kg, p = 0.037). The elimination rate of theophylline increased after parenteral feeding reflected by an increase in the elimination rate constant (0.06 h-1, 95 percent CI 0.01-0.10 h-1, p = 0.023). CONCLUSIONS This study suggests that parenteral nutrition using a glucose-based solution acutely influences theophylline disposition in malnourished patients.