Serum/Saliva Correlations for Theophylline in Asthmatics

Abstract

Theophylline levels in mixed saliva (both stimulated and unstimulated) were compared with total and free (unbound) serum theophylline levels in 28 asthmatic outpatients using theophylline regularly. Stimulated saliva predicted both total and unbound serum theophylline concentrations within +/- 1 microgram/mL in 62.5% and 92.9%, respectively, of the samples examined. In addition, the total serum levels could be used to predict unbound serum concentrations to within +/- 1 mg/L in 100% of the cases that were examined. These results indicate that saliva levels predict the unbound serum theophylline levels with greater accuracy and precision than they predict total serum theophylline levels. In addition, total serum levels can be used to reliably predict unbound serum levels. The use of mixed stimulated saliva is recommended as a reliable non-invasive method for monitoring unbound serum theophylline levels. The therapeutic range for saliva, which corresponds to the accepted total serum concentration range of 10-20 mg/L, is approximately 5.6-11.3 mg/L.

The Use of Oral Fluid for Therapeutic Drug Management

“…Saliva pH and saliva protein binding were not considered to be significant influences on observed variability 74 and the saliva to free plasma drug approached unity 75 . Several studies attempting to develop correlation equations to predict plasma levels from oral fluid measurement of drug concentrations have been able to predict plasma levels within 2 μg/mL 76–78 . Precision was better for the saliva to free plasma theophylline.…”

“…75 Several studies attempting to develop correlation equations to predict plasma levels from oral fluid measurement of drug concentrations have been able to predict plasma levels within 2 g/mL. [76][77][78] Precision was better for the saliva to free plasma theophylline. Others found that stimulated saliva samples improved the correlation sufficiently between saliva and free fraction in serum so that saliva-based predictions of theophylline levels could be made in adults with asthma 74 or with chronic airflow obstruction.…”

Therapeutic Drug Monitoring in Saliva

“…Many later studies support the conclusions that the CsaJ/Cup exhibits acceptable variability, pH and concentration independence and a high degree of utility for predicting Cup (Blanchard et al 1991;Ebden et al 1985;Siegel et al 1990;Stoehr et al 1986). The data from these studies are summarised in table II.…”