RELATION BETWEEN PLASMA AND SALIVA CONCENTRATIONS OF ENOXACIN, CIPROFLOXACIN, AND THEOPHYLLINE

To assess the reliability of predicting plasma concentrations of enoxa cin, ciprofloxacin, and theophylline from drug concentrations in saliv a, six healthy volunteers received single oral doses of enoxacin, cipr ofloxacin, and theophylline administered in combination on each of fou r separate study days, with different doses separated by at least 5 da ys. Drug concentrations were determined by a newly developed high-perf ormance liquid chromatography (HPLC) assay, which could measure simult aneously all three drugs in plasma or saliva. Saliva data from the pos tabsorptive phase after drug administration were used to minimize the effects of variation in absorption. There were good correlations betwe en saliva and plasma concentrations of enoxacin, ciprofloxacin, and th eophylline (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 r atios 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 c oncentrations of enoxacin and ciprofloxacin are not reliable for predi cting plasma concentrations. However, saliva may be used reliably for predicting plasma concentrations of theophylline.