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Plasma concentrations of 5-fluorouracil and F-beta-alanine following oral administration of S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, as compared with protracted venous infusion of 5-fluorouracil.

Yamada Y, Hamaguchi T, Goto M, Muro K, Matsumura Y, Shimada Y, Shirao K, Nagayama S - Br. J. Cancer (2003)

Bottom Line: The AUC(0-10 h) of FBAL on day 5 of PVI of 5-FU was 9465+/-3225 ng h ml(-1), AUC(0-10 h), as compared with 1725+/-605 ng h ml(-1) on day 5 of S-1 treatment.The AUC(0-10 h) of uracil on day 5 was 252+/-60 ng h ml(-1) with PVI of 5-FU and 12 582+/-3060 ng h ml(-1) with S-1.The AUC(0-10 h) of FBAL was markedly lower and plasma uracil concentrations were significantly higher for S-1 than for PVI of 5-FU, clearly demonstrating the effect of DPD inhibition.

View Article: PubMed Central - PubMed

Affiliation: Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. yayamada@ncc.go.jp

ABSTRACT
The pharmacokinetics and pharmacodynamics of oral S-1, a dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine, were compared with those of protracted venous infusion (PVI) of 5-fluorouracil (5-FU). In all, 10 patients with gastric cancer received PVI of 5-FU at a dose of 250 mg m(-2) day(-1) for 5 days. After a washout period of 9 days, the patients received two divided doses daily for 28 days. S-1 was administered orally at about 0900 and 1900 hours. The daily dose of S-1 in terms of tegafur was 80 mg day(-1) in patients with a body surface area (BSA) of <1.25 m(2), 100 mg day(-1) in those with a BSA of >or=1.25 m(2) to <1.5 m(2), and 120 mg day(-1) in those with a BSA of >or=1.5 m(2). Plasma concentrations of 5-FU and F-beta-alanine (FBAL) were measured for pharmacokinetic analysis, and the plasma uracil concentration was monitored as a surrogate marker of DPD inhibition (pharmacodynamic analysis) in the same patients on days 1-5 of PVI of 5-FU and on days 1-5 of oral S-1. The area under the curve (AUC(0-10 h)) of 5-FU on day 5 was 728+/-113 ng h ml(-1) for PVI of 5-FU and 1364+/-374 ng h ml(-1) for S-1. The median 5-FU PVI : S-1 ratio of the AUC(0-10 h) of 5-FU was 1.9. The AUC(0-10 h) of FBAL on day 5 of PVI of 5-FU was 9465+/-3225 ng h ml(-1), AUC(0-10 h), as compared with 1725+/-605 ng h ml(-1) on day 5 of S-1 treatment. The AUC(0-10 h) of uracil on day 5 was 252+/-60 ng h ml(-1) with PVI of 5-FU and 12 582+/-3060 ng h ml(-1) with S-1. The AUC(0-10 h) of FBAL was markedly lower and plasma uracil concentrations were significantly higher for S-1 than for PVI of 5-FU, clearly demonstrating the effect of DPD inhibition.

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Plasma concentrations of 5-FU and uracil vs time after PVI of 5-FU and after oral S-1. Closed and open circles show the concentration of 5-FU and concentration of uracil, respectively. The left and right graphs show data for PVI of 5-FU and for S-1, respectively. Data are presented as means; bars, s.d.
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fig1: Plasma concentrations of 5-FU and uracil vs time after PVI of 5-FU and after oral S-1. Closed and open circles show the concentration of 5-FU and concentration of uracil, respectively. The left and right graphs show data for PVI of 5-FU and for S-1, respectively. Data are presented as means; bars, s.d.

Mentions: The plasma concentrations of 5-FU, uracil, and FBAL after administration of PVI 5-FU and oral S-1 in the 10 patients on days 1–5 are shown in Figures 1Figure 1


Plasma concentrations of 5-fluorouracil and F-beta-alanine following oral administration of S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, as compared with protracted venous infusion of 5-fluorouracil.

Yamada Y, Hamaguchi T, Goto M, Muro K, Matsumura Y, Shimada Y, Shirao K, Nagayama S - Br. J. Cancer (2003)

Plasma concentrations of 5-FU and uracil vs time after PVI of 5-FU and after oral S-1. Closed and open circles show the concentration of 5-FU and concentration of uracil, respectively. The left and right graphs show data for PVI of 5-FU and for S-1, respectively. Data are presented as means; bars, s.d.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2394492&req=5

fig1: Plasma concentrations of 5-FU and uracil vs time after PVI of 5-FU and after oral S-1. Closed and open circles show the concentration of 5-FU and concentration of uracil, respectively. The left and right graphs show data for PVI of 5-FU and for S-1, respectively. Data are presented as means; bars, s.d.
Mentions: The plasma concentrations of 5-FU, uracil, and FBAL after administration of PVI 5-FU and oral S-1 in the 10 patients on days 1–5 are shown in Figures 1Figure 1

Bottom Line: The AUC(0-10 h) of FBAL on day 5 of PVI of 5-FU was 9465+/-3225 ng h ml(-1), AUC(0-10 h), as compared with 1725+/-605 ng h ml(-1) on day 5 of S-1 treatment.The AUC(0-10 h) of uracil on day 5 was 252+/-60 ng h ml(-1) with PVI of 5-FU and 12 582+/-3060 ng h ml(-1) with S-1.The AUC(0-10 h) of FBAL was markedly lower and plasma uracil concentrations were significantly higher for S-1 than for PVI of 5-FU, clearly demonstrating the effect of DPD inhibition.

View Article: PubMed Central - PubMed

Affiliation: Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. yayamada@ncc.go.jp

ABSTRACT
The pharmacokinetics and pharmacodynamics of oral S-1, a dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine, were compared with those of protracted venous infusion (PVI) of 5-fluorouracil (5-FU). In all, 10 patients with gastric cancer received PVI of 5-FU at a dose of 250 mg m(-2) day(-1) for 5 days. After a washout period of 9 days, the patients received two divided doses daily for 28 days. S-1 was administered orally at about 0900 and 1900 hours. The daily dose of S-1 in terms of tegafur was 80 mg day(-1) in patients with a body surface area (BSA) of <1.25 m(2), 100 mg day(-1) in those with a BSA of >or=1.25 m(2) to <1.5 m(2), and 120 mg day(-1) in those with a BSA of >or=1.5 m(2). Plasma concentrations of 5-FU and F-beta-alanine (FBAL) were measured for pharmacokinetic analysis, and the plasma uracil concentration was monitored as a surrogate marker of DPD inhibition (pharmacodynamic analysis) in the same patients on days 1-5 of PVI of 5-FU and on days 1-5 of oral S-1. The area under the curve (AUC(0-10 h)) of 5-FU on day 5 was 728+/-113 ng h ml(-1) for PVI of 5-FU and 1364+/-374 ng h ml(-1) for S-1. The median 5-FU PVI : S-1 ratio of the AUC(0-10 h) of 5-FU was 1.9. The AUC(0-10 h) of FBAL on day 5 of PVI of 5-FU was 9465+/-3225 ng h ml(-1), AUC(0-10 h), as compared with 1725+/-605 ng h ml(-1) on day 5 of S-1 treatment. The AUC(0-10 h) of uracil on day 5 was 252+/-60 ng h ml(-1) with PVI of 5-FU and 12 582+/-3060 ng h ml(-1) with S-1. The AUC(0-10 h) of FBAL was markedly lower and plasma uracil concentrations were significantly higher for S-1 than for PVI of 5-FU, clearly demonstrating the effect of DPD inhibition.

Show MeSH
Related in: MedlinePlus