Total plasma and mixed stimulated saliva theophylline concentrations (by high performance liquid chromatography) and free plasma theophylline concentrations (by equilibrium dialysis) were measured in simultaneously collected samples from 32 outpatients receiving chronic oral theophylline treatment, who had received the drug at least two hours before sampling. There was a close relationship between saliva and total plasma theophylline concentration and between total saliva and free plasma concentration. The mean saliva to total plasma drug concentration ratio was 0.69 (SE 0.09) and the mean difference between paired saliva and free plasma concentration was 0.65 (0.17) microgram/ml. It is concluded that stimulated mixed saliva provides a simple, non-invasive method of assessing total (and free) plasma theophylline concentrations during chronic oral treatment. The therapeutic range for saliva, corresponding to the generally accepted total plasma concentration range (10-20 micrograms/ml), is approximately 7-14 micrograms/ml.
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