PP129: Sirolimus levels in blood vs. saliva in chronically treated patients – A rational basis for topical use

Purpose Sirolimus, currently used as an immunosuppressant, is a potent mammalian target of rapamycin blocker with antiproliferative activity. Its potential for the management of oral pathologies and cancer and has been suggested. Topical application in the oral cavity can enhance availability and efficacy of the drug. The objective of this study was to establish an analytical method for determining sirolimus levels in human saliva in those using sirolimus chronically as well as calculation of the blood vs. saliva ratio. Materials and methods Chemiluminescent microparticle immunoassay technology was used to determine blood and saliva levels of sirolimus in kidney transplant patients. All patients signed informed consent forms and an examination of the oral cavity was performed, clinical findings and oral symptoms, if any, were recorded along with the medical status of the patient. Blood and saliva samples were collected at the same time and analyzed. The study was approved by the institutional review board. Results An analytical method for determining sirolimus levels in human saliva was established. Four patients were enrolled in the study. In all patients medication blood levels were stable. None of the patients had pathological lesions in their oral cavities. A substantial variability was observed among samples. No linear correlation was found. The saliva levels were on average four times lower than blood levels. Conclusions The sensitive Chemiluminescent microparticle immunoassay method determined sirolimus levels both in saliva and blood in treated patients. Sirolimus saliva levels are significantly lower than blood levels.These results emphasize the need for delivery methods with better oral topical biological availability and reinforce the rationale for using sirolimus topically for the treatment of responsive oral pathologies.