Gemcitabine and Epirubicin Plasma Concentration-Related Excretion in Saliva in Patients With Non-Small Cell Lung Cancer

Aim: The excretion in saliva of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as well as epirubicin (Epi) and its metabolite epirubicinol (Epi-ol) was studied in patients with non-small cell lung cancer, treated with gemcitabine plus epirubicin.

Methods: Patients (n = 12) were treated with gemcitabine 1125 mg/m(2), followed by Epi 100 mg/m(2). Blood, saliva, and oral mucosa cells were collected during 22 hours for analysis of gemcitabine, Epi, and their metabolites. Gemcitabine, dFdU, Epi, and Epi-ol were quantified by high-performance liquid chromatography.

Results: Gemcitabine was cleared rapidly from plasma and undetectable after 3 hours in all patients. Gemcitabine was detectable in saliva during only the first hour after infusion. The C(max) in saliva was 0.66 +/- 0.61 mg/L, and the saliva to plasma ratio (S/P ratio) was 0.038 +/- 0.037. The C(max) of dFdU was reached 1.5-2 hours after gemcitabine infusion and was 1.03 +/- 0.63 mg/L. The dFdU S/P ratios gradually increased from 0.021 +/- 0.013 at t = 1 hour to 0.050 +/- 0.027 at t = 6 hours after infusion. Epi displayed a triexponential plasma concentration-time profile. The Epi and Epi-ol concentrations in saliva at t = 6 hours after administration were 55 6 27 and 9 +/- 9 mu g/L, respectively, and decreased to 28 +/- 14 and 7 +/- 4 mu g/L, respectively, at t = 22 hours. The corresponding S/P ratios were 1.28 +/- 0.73 and 0.36 +/- 0.31 at t = 6 hours and 1.72 +/- 1.00 and 0.62 +/- 0.34 at t = 22 hours, respectively. The amount of Epi in mucosal cells ranged from 135-598 ng per 10(6) cells at t = 3 hours and decreased to 33-196 ng per 10(6) cells at t = 22 hours.

Conclusion: Gemcitabine and Epi, as well as their main metabolites dFdU and Epi-ol, are excreted in detectable amounts in saliva, although their absolute concentrations remain relatively low.