A pharmacodynamic and pharmacokinetic study of fluoropyrimidines in a nude mouse system and in postoperative patients with gastric cancer.

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Inada T, Ogata Y, Kubota T, Ozawa I, Hishinuma S, Shimizu H, Kotake K, Ikeda T, Koyama Y

A pharmacodynamic and pharmacokinetic study of fluoropyrimidines in a nude mouse system and in postoperative patients with gastric cancer.

Surg Today. 1993;23(8):687-92.

PubMed ID
8400672 [ View in PubMed
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Abstract

To evaluate the effect of the oral fluoropyrimidines, tegafur and uracil (UFT) and 5-fluorouracil (5-FU), a pharmacodynamic analysis was conducted using a nude mouse system and patients. In the nude mouse system, UFT and 5-FU showed similar marginal effects against the human tumor xenograft Co-4, and the concentration of 5-FU in serum 1 h after the last administration being 0.04 micrograms/ml, which was assumed to be the minimum effective concentration. (MEC). Postoperative patients were subdivided into three groups, being: those who underwent subtotal gastrectomy and received UFT; those who underwent subtotal gastrectomy and received 5-FU; and those who underwent total gastrectomy and received UFT. In the UFT groups, the concentration of 5-FU in the portal and peripheral blood showed similar elimination in terms of the peak concentration (Cmax) and the area under the curve (AUC). In the 5-FU groups, the AUC and Cmax were significantly higher in portal blood than peripheral blood. The concentrations in the portal blood of the 5-FU group and in the portal and peripheral blood of the UFT group were significantly higher than the MEC (0.04 micrograms/ml). From these pharmacodynamic data, it was concluded that postoperative chemotherapy with oral fluoropyrimidines can achieve the MEC in portal and peripheral blood.

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