Gemcitabine and epirubicin plasma concentration-related excretion in saliva in patients with non-small cell lung cancer.

Abstract

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, followed by Epi 100 mg/m. 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 Cmax in saliva was 0.66 +/- 0.61 mg/L, and the saliva to plasma ratio (S/P ratio) was 0.038 +/- 0.037. The Cmax 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 +/- 27 and 9 +/- 9 microg/L, respectively, and decreased to 28 +/- 14 and 7 +/- 4 microg/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 cells at t = 3 hours and decreased to 33-196 ng per 10 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.

• Authors: Jan Gerard Maring, Floris M Wachters, Marina Maurer, Donald R A Uges, Elisabeth G E de Vries, Harry J M Groen
• Journal: Therapeutic drug monitoring (Ther Drug Monit) Vol. 32 Issue 3 Pg. 364-8 (Jun 2010) ISSN: 1536-3694 [Electronic] United States
• PMID: 20335827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Deoxycytidine
• Epirubicin
• Gemcitabine

Topics

• Antimetabolites, Antineoplastic (blood)
• Carcinoma, Non-Small-Cell Lung (blood, metabolism, pathology)
• Chromatography, High Pressure Liquid (methods)
• Deoxycytidine (analogs & derivatives, blood, metabolism)
• Epirubicin (blood, metabolism)
• Humans
• Infusions, Intravenous
• Lung Neoplasms (blood, metabolism, pathology)
• Saliva (chemistry)
• Gemcitabine