A pharmacodynamic and pharmacokinetic study of fluoropyrimidines in a nude mouse system and in postoperative patients with gastric cancer.
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.
Inada
T
T
Department of Surgery, Tochigi Cancer Center, Japan.
Ogata
Y
Y
Kubota
T
T
Ozawa
I
I
Hishinuma
S
S
Shimizu
H
H
Kotake
K
K
Ikeda
T
T
Koyama
Y
Y
D000230:Adenocarcinoma / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism; D005472:Fluorouracil / Q000493:pharmacokinetics*; D005743:Gastrectomy; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000601:surgery*; D005641:Tegafur / Q000493:pharmacokinetics; D014498:Uracil / Q000493:pharmacokinetics*
D005641:Tegafur; D014498:Uracil; D005472:Fluorouracil