Determination of theophylline in saliva, using fluorescence polarization immunoassay (FPIA)

Theophylline concentrations were determined by fluorescence polarization immunoassay (FPIA) in saliva, serum and serum water of healthy volunteers and outpatients after administration of single theophylline doses, and after the administration of several doses in order to establish a steady state. The FPIA allowed rapid and reliable theophylline determinations in saliva and serum water (between-days coefficients of variation: less than 3%; recovery: 95-03%). Salivary theophylline concentrations measured by FPIA in 30 samples agreed well with those determined by HPLC. Furthermore the results obtained by ultrafiltration for the concentration of unbound theophylline in serum water were in good agreement with those determined by ultracentrifugation. The binding of theophylline by serum protein rose by about 25%, when the pH of the samples was increased from 7.0 to 8.0. After adjusting the pH to 7.4, average values for theophylline binding to proteins at 25 degrees C ranged from 48.5 to 52.2% in serum samples from outpatients and healthy adults. Salivary theophylline concentrations correlated well with total and free serum theophylline concentrations in healthy adults and outpatients (r = 0.90-0.98). The theophylline concentration in saliva was on average about 20-30% higher than the unbound theophylline concentration in serum water. The saliva/serum concentration ratio of theophylline showed some intersubject variation (0.68 +/- 0.08; range: 0.50-0.85). Using the mean saliva/serum concentration ratio of the patient group, steady state serum theophylline concentrations were predicted from salivary levels with a mean error of 7.6% (range: 0.0-26.8%). The salivary theophylline concentration appears to be a suitable parameter for assessment of compliance, for identification of patients with inappropriate dosage, and for consequent dosage adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)