Interpretive Handbook

Test 8661 :
Theophylline, Serum

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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.

Useful For Suggests clinical disorders or settings where the test may be helpful

Assessing and adjusting dosage for optimal therapeutic level


Assessing toxicity

Interpretation Provides information to assist in interpretation of the test results

Response to theophylline is directly proportional to serum level.


Patients usually receive the best response when the level is >10.0 mcg/mL, with minimal toxicity experienced as long as the level is <20.0 mcg/mL.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Many drugs affect the plasma level of this drug (as outlined in Clinical Information).

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


Children and adults: 8.0-20.0 mcg/mL

Neonatal apnea: 6.0-11.0 mcg/mL

Toxic concentration: > or =20.0 mcg/mL

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Pesce AJ, Rashkin M, Kotagal U: Standards of laboratory practice: theophylline and caffeine monitoring. Clin Chem 1998, May;44(5);1124-1128

2. McCudden CR, Broussard LA: Caffeine, lithium and theophylline. In Therapeutic Drug Monitoring Data: A Concise Guide. Third edition. Edited by CA Hammett-Stabler, A Dasgupta, AACC Press, 2007

3. Vassallo R, Lipsky JJ: Theophylline: recent advances in the understanding of its mode of action and uses in clinical practice. Mayo Clin Proc 1998;73:346-354