Comparison of Methods for Determining Unbound Theophylline Concentrations

Abstract

In order to determine the suitability of using tears and saliva to estimate theophylline concentrations, simultaneous plasma, tear, and saliva samples were obtained in 22 adult male patients taking theophylline. Unbound theophylline concentrations were determined by equilibrium dialysis for nine of the subjects and compared with the concentrations determined in saliva and tears. The mean tear/unbound and saliva/unbound ratios were 0.94 ± 0.12, r = 0.88, and 1.25 ± 0.14, r = 0.91, respectively. Tear/plasma ratios ranged from 0.36 to 0.76 (mean 0.58 ± 0.11), and tear concentrations correlated well with plasma concentrations (r = 0.94). Saliva/plasma ratios ranged from 0.52 to 1.16 (mean 0.79 ± 0.19), and there was a positive correlation between plasma and saliva concentrations (r = 0.84). The mean tear/unbound and saliva/unbound ratio predicted the unbound concentration within 1 μg/ml in 50 and 78% of the cases, respectively. Saliva and tears have limited clinical value in estimating the unbound concentration of theophylline.