Comparative monitoring of oral theophylline treatment in blood serum, saliva, and nasal mucus

Ther Drug Monit. 2012 Apr;34(2):217-21. doi: 10.1097/FTD.0b013e3182492a20.


Background: Theophylline, used in the treatment for various pulmonary pathologies, is usually given orally with drug levels measured primarily in blood serum and occasionally in saliva. Although theophylline treatment is now not commonly used it has been effective to correct smell loss (hyposmia). This is important because 21 million people in the United States exhibit hyposmia and oral theophylline has corrected hyposmia in about 50% of these patients. This result suggests that oral theophylline may result in the drug not only appearing in the serum but also in nasal mucus, thereby playing a role in correcting hyposmia. No prior report of theophylline in nasal mucus has been made and no comparison of levels in nasal mucus, blood serum, or saliva has been previously reported.

Purpose: The aim was to determine, after oral theophylline treatment, if it is present in nasal mucus and, if present, to compare the levels with those in serum and saliva.

Methods: Oral theophylline was given to 23 hyposmic patients at daily doses of 200, 300, 400, 600, and 800 mg for periods of 2-10 months. During each period, blood serum, saliva, and nasal mucus were collected and theophylline measured in each fluid.

Results: Theophylline was found in nasal mucus and in saliva and blood serum at each drug dose in each patient to whom it was given. The mean level of theophylline in nasal mucus was 74% that of serum; mean level in saliva was 67% of serum; mean level in nasal mucus was 111% that in saliva.

Conclusions: Theophylline is present in nasal mucus after oral administration. Levels in nasal mucus reflect blood and saliva levels in a consistent manner and offer a simple convenient noninvasive method to monitor theophylline doses of the oral drug.

Publication types

  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nasal Mucosa / chemistry
  • Olfaction Disorders / drug therapy*
  • Olfaction Disorders / epidemiology
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / pharmacokinetics*
  • Phosphodiesterase Inhibitors / therapeutic use
  • Saliva / chemistry
  • Theophylline / administration & dosage
  • Theophylline / pharmacokinetics*
  • Theophylline / therapeutic use
  • Tissue Distribution
  • United States / epidemiology


  • Phosphodiesterase Inhibitors
  • Theophylline