Clinical Information

Theophylline and its congener, aminophylline, are used to relax smooth muscles of the bronchial airways and pulmonary blood vessels to relieve and prevent symptoms of asthma and bronchospasm.

Theophylline is administered orally at a dose of 400 mg/day or 6 mg/kg, whichever is lower, or intravenously as aminophylline at 0.6 mg/kg/hour. Oral dosage may be increased at 200-mg increments to a maximum of 900 mg/day, or 13 mg/kg if the steady-state blood concentration is within the therapeutic range of 10.0 to 20.0 mcg/mL.

Theophylline has a half-life of 4 hours in children and adult smokers, and 7 hours in nonsmoking adults, thus steady-state is reached in approximately 1 day. The volume of distribution is 0.5 L/kg, and the drug is approximately 50% protein bound. Theophylline exhibits zero-order clearance kinetics like phenytoin, small increases in dose yield disproportionately large increases in blood concentration.

Coadministration of cimetidine and erythromycin will significantly inhibit theophylline clearance, requiring dosage reduction. Other drugs such as allopurinol, ciprofloxacin, oral contraceptives, and propranolol inhibit theophylline clearance to a lesser degree.

Smoking induces the synthesis of cytochrome P448, the antipyrine-dependent cytochrome, which significantly increases the rate of metabolism of theophylline. Drugs such as phenobarbital, phenytoin, carbamazepine, and rifampin slightly increase the rate at which the drug is cleared.

Theophylline exhibits rather severe toxicity that is proportional to blood level.