부산대학교 도서관

BACKGROUND:: Most cancer patients treated with everolimus experience stomatitis, which seriously affects the quality of life. The salivary concentrations of everolimus may predict the incidence and severity of stomatitis. The authors aimed to examine whether it was feasible to quantify the everolimus concentration in saliva and subsequently use it to predict stomatitis. METHODS:: Saliva and whole blood samples were taken from cancer patients, who were treated with everolimus in the dosage of either 10 mg once a day or 5 mg twice a day. Everolimus concentrations in saliva samples were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). A published population pharmacokinetic model was extended with the everolimus concentration in saliva, to assess any association between everolimus in the blood and saliva. Subsequently, the association between the occurrence of stomatitis and the everolimus concentration in saliva was studied. RESULTS:: Eleven patients were included in the study; saliva samples were available from 10 patients, including three patients with low-grade stomatitis. Everolimus concentrations were more than 100-fold lower in saliva than in whole blood (accumulation ratio 0.00801; relative standard error 32.5%). Inter-individual variability (67.7%) and residual unexplained variability (84.0%) were high. The salivary concentration of everolimus tended to be higher in patients with stomatitis, 1 h post-dose (p = 0.14). CONCLUSIONS:: Quantification of the everolimus concentration in saliva was feasible and revealed a non-significant correlation between everolimus concentration in the saliva and the occurrence of stomatitis. If future research proves this relationship to be significant, the everolimus concentration in the saliva may be used as an early predictor of stomatitis without invasive sampling. Thereby, in patients with high salivary everolimus concentrations, precautions can be taken to decrease the incidence and severity of stomatitis.