INFLUENCE OF LOCAL RADIOTHERAPY ON PENETRATION OF FLUCONAZOLE INTO HUMAN SALIVA

The pharmacokinetics of fluconazole (50 mg, single oral dose) in saliv a and plasma were determined for five healthy subjects and five patien ts who underwent radiotherapy (dose, >45 Gy over a 6-week period) in t he salivary gland area and suffered from oropharyngeal candidiasis. Sa liva was collected after electrical stimulation. Fluconazole was measu red by liquid chromatography. From healthy volunteers and patients, sa liva and plasma were sampled from 0 to 24 h. Although fluconazole pene tration kinetics were significantly slowed down in irradiated patients , saliva concentrations of fluconazole were higher than those in the p lasma, except al 1 h. In the postdistribution phase, the saliva/plasma concentration ratio was in the range of 1.2 to 1.4, and there was no significant difference between healthy subjects and patients. The sali va concentration of fluconazole was over 1 mg/liter throughout the ent ire interval 2 to 24 h after drug intake. From these results, the clin ical efficacy of fluconazole for oropharyngeal candidiasis is not expe cted to be less than that in subjects with normal salivary glands, pro vided that salivary secretion remains.