Levels of sirolimus in Saliva vs. Blood - the rationale of topical oral use for oral malignancy

Background: Sirolimus is a potent blocker of mammalian target of Rapamycin (MTOR), with anti proliferative activity. Its potential for the management of oral cancer has been suggested. Our aim was to establish an analytical method for determining sirolimus levels in human saliva and to calculate the blood vs. saliva ratio in individuals using sirolimus chronically in order to evaluate the total oral tissue exposure. Patients and Methods: Chemiluminescent microparticle immunoassay technology (CMIA) was used to determine the blood and saliva levels of sirolimus in four transplant patients chronically-treated with sirolimus. Results: An analytical method for determining sirolimus levels in human saliva was established. We demonstrated that saliva levels were on average six times lower than blood levels. Conclusion: The specific sensitive analytical method showed that the saliva levels of sirolimus are significantly lower than blood levels, thus reinforcing the rationale for the use of topical oral sirolimus to enhance availability, efficacy and safety for treating oral malignancies.