Relation Between Plasma and Saliva Concentrations of Enoxacin, Ciprofloxacin, and Theophylline

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Abstract
To assess the reliability of predicting plasma concentrations of enoxacin, ciprofloxacin, and theophylline from drug concentrations in saliva, six healthy volunteers received single oral doses of enoxacin, ciprofloxacin, and theophylline administered in combination on each of four separate study days, with different doses separated by at least 5 days. Drug concentrations were determined by a newly developed high-performance liquid chromatography (HPLC) assay, which could measure simultaneously all three drugs in plasma or saliva. Saliva data from the postabsorptive phase after drug administration were used to minimize the effects of variation in absorption. There were good correlations between saliva and plasma concentrations of enoxacin, ciprofloxacin, and theophylline (r = 0.91, 0.88, and 0.98, respectively). The mean (±SD) saliva-to-plasma (S/P) ratio for theophylline was 0.63 ± 0.06 with a coefficient of variation (CV) of 7.9 ± 2.7%. In contrast, the S/P ratios and CV values for enoxacin and ciprofloxacin were 0.72 ± 0.21 and 28.9 ± 11.1%, and 0.58 ± 0.15 and 25.3 ± 6.7%, respectively. Because of the large inter- and intraindividual variability, saliva concentrations of enoxacin and ciprofloxacin are not reliable for predicting plasma concentrations. However, saliva may be used reliably for predicting plasma concentrations of theophylline.