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J.Health Sci., 56(6), 684-689, 2010
-Regular Article-
Feasibility of Bioavailability Testing by Simultaneous Determination of Serum Concentrations of Tegafur and 5-fluorouracil after TS-1 Oral or Tube Administration for Chemotherapy in Oral Cancer Patients
Mio Nakamoto,*, a, b Hitoshi Ishigouoka,a
Kazumichi Sato,c Tomohiro Yamauchi,c
Morio Tonogi,d Gen-yuki Yamane,c, d
Yoichi Tanaka,e Hideaki Ichiba,b
Takeshi Fukushima,b and Yoshio Inouyeb
aDepartment of Pharmacy, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan,
bFaculty of Pharmaceutical Sciences Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan,
cOral Cancer Center,
dDepartment of Oral Medicine, Oral and Maxillofacial Surgery and
eClinical Laboratory, Division of Surgical Pathology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
TS-1 is an oral anticancer agent comprising three components: two biochemical modulators of 5-fluorouracil (5-FU) and tegafur (FT), a prodrug of 5-FU. TS-1 displays potent anti-tumor activity by maintaining effective 5-FU concentrations in serum for a prolonged period. FT is gradually converted to 5-FU in vivo via 5'-hydroxylation mediated by cytochrome P450s. As a result, genetic polymorphisms can cause wide individual differences in serum concentration of 5-FU after administration of TS-1, requiring monitoring of serum concentration of 5-FU for each patient. Chemotherapy with TS-1 plays a major role in the treatment of oral cancer. In cases where a patient with oral cancer shows dysphagia, TS-1 may need to be tube-administered. Although tube administration by the simple suspension method has been recommended from a biosafety perspective, particularly for anti-cancer agents, its efficacy remains unclear. We established a simple high-performance liquid chromatography method for simultaneous determination of FT and 5-FU levels at clinical sites by modifying a method reported in the literature.1) Unlike the original method, this simplified method does not require extraction procedures to separate FT and 5-FU, and requires only 250 μl of serum. Using this method, we compared FT concentrations in the sera of oral cancer patients administered TS-1 orally or via a tube-assisted simple suspension method. No significant differences in FT concentrations were apparent between these two modes of administration. TS-1 treatment by tube administration using the simple suspension method thus seems useful for patients with dysphagia as an alternative to oral dosage.
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