Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients

Abstract

Background S-1 is an oral anticancer drug composed of tegafur (FT), which is a prodrug of 5-FU, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate. Recently, some studies have been reported on watering eyes caused by S-1. However, the mechanism of watering eyes caused by S-1 is still unclear. The aim of this study was to investigate the correlation between tears and plasma concentrations of FT, 5-FU, and CDHP, which are components and active modulator of S-1. Methods We prospectively investigated the pharmacokinetics (PK) of FT, 5-FU, and CDHP in plasma and in tears of gastric cancer patients who were treated with S-1 monotherapy at the dose of 80 mg/m 2 /day. Plasma and tears from both eyes were obtained 1, 2, 4, and 8 h after S-1 administration on day 1 and 14 of the first cycle. Results Total of eight patients were enrolled. All the FT, 5-FU and CDHP were detected both in plasma and in tears, and their PK parameters were measured. There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears on day 1 and day 14 (correlation coefficients r , right eye/left eye: r = 0.882/0.878, 0.877/0.890, and 0.885/0.878, respectively). Conclusion There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears. The result is expected to facilitate the further investigation into the causes of watering eyes and the establishment of the effective methods for the prevention and the treatment.

Current Status of Therapeutic Drug Monitoring of 5-Fluorouracil Prodrugs

“…Lacrimal tract disorders caused by S-1 are well-known adverse events. Yasui measured drug concentrations in the plasma and tears, and demonstrated that 5-FU and gimeracil concentrations exhibit a positive correlation (44). This report is expected to contribute to the establishment of preventive measures for lacrimal disorders.…”