Theophylline, Serum

Theophylline, Serum

CPT Test code: 80198

Specimen: Serum or plasma
Volume: 1 mL
Minimum Volume: 0.3 mL
Container: Red-top tube or green-top (heparin) tube. Do not use a gel-barrier tube. The use of gel-barrier tubes is not recommended due to slow absorption of the drug by the gel. Depending on the specimen volume and storage time, the decrease in drug level due to absorption may be clinically significant.
Collection: Transfer separated serum or plasma to a plastic transport tube. Trough: immediately prior to next dose; after change in dose: children: two days, adults: one to two days.
Storage Instructions: Refrigerate
Causes for Rejection: Gel-barrier tube; hemolysis; gross lipemia; icteric specimen
Reference Interval: Therapeutic: neonatal: 5.0-10.0 μg/mL, adults: 10.0-20.0 μg/mL
Critical Values: Potentially toxic: neonatal: >10.0 μg/mL, adults: >20.0 μg/mL
Additional Information: Theophylline is prescribed for bronchial asthma, for chronic obstructive pulmonary disease, and for newborn apnea. The drug is extensively metabolized1 with peak serum levels reached four hours after oral dose. Troleandomycin and erythromycin may slow theophylline elimination. Heart failure, liver disease, prolonged fever, certain infections, and obesity may have similar effects. Prolonged half-life occurs in premature infants. Dosage should be reduced in these situations.

By contrast, half-life is shortened in smokers, variable with phenobarbital administration; higher doses are also tolerated in acidemia. Smokers on the average are reported to need 1.5 to 2 times as much of the drug as nonsmokers to achieve the same effects. Optimal resampling time after change in dosage is 48 hours for adults, one to two days for children. The half-life of theophylline is from 3 to 10 hours for adults and 1.4 to 7.9 hours for children, but varies between individuals.

Studying serum concentrations and toxic effects, Bertino et al found toxicity with peak theophylline concentrations as low as 19.4 mg/L. Recognizing theophylline toxicity over a wide range of theophylline levels, these authors questioned the association between the severity of toxic effects and serum concentrations.2 Aitken and Martin also found lack of correlation between serum theophylline level and toxic effects.3

Blood levels should be interpreted in light of the patient’s clinical status and use of other medications.

Toxic effects include nausea, vomiting, diarrhea, headache, atrial and ventricular arrhythmias, tremors, and convulsions.

Footnotes: 1. Smith FA, “Theophylline Drug Monitoring of Theophylline, Salicylates, and Acetaminophen,” Clin Lab Med, 1981, 1(3):559-79 (review). PubMed 7049527

2. Bertino JS Jr, Walker JW, “Reassessment of Theophylline Toxicity: Serum Concentrations, Clinical Course, and Treatment,” Arch Intern Med, 1987, 147(4):757-60. PubMed 3827463

3. Aitken ML, Martin TR, “Life-Threatening Theophylline Toxicity Is not Predictable by Serum Levels,” Chest, 1987, 91(1):10-4.PubMed 3792059