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Two Dosages of Oral Fluoropyrimidine S-1 of 35 and 40 mg/m(2) bid: Comparison of the Pharmacokinetic Profiles in Korean Patients with Advanced Gastric Cancer

OBJECTIVE: In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after administration of S-1 at 35 or 40 mg/m(2) bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric ca...

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Autores principales: Jeung, Hei-Cheul, Rha, Sun Young, Shin, Sang Joon, Ahn, Joong Bae, Noh, Sung Hoon, Roh, Jae Kyung, Chung, Hyun Cheol
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800316/
https://www.ncbi.nlm.nih.gov/pubmed/19880858
http://dx.doi.org/10.1093/jjco/hyp124
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author Jeung, Hei-Cheul
Rha, Sun Young
Shin, Sang Joon
Ahn, Joong Bae
Noh, Sung Hoon
Roh, Jae Kyung
Chung, Hyun Cheol
author_facet Jeung, Hei-Cheul
Rha, Sun Young
Shin, Sang Joon
Ahn, Joong Bae
Noh, Sung Hoon
Roh, Jae Kyung
Chung, Hyun Cheol
author_sort Jeung, Hei-Cheul
collection PubMed
description OBJECTIVE: In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after administration of S-1 at 35 or 40 mg/m(2) bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric cancer. METHODS: Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m(2), ranging from 70 to 88 mg/m(2). RESULTS: Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. C(max) and AUC(0–48 h) values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity. CONCLUSIONS: We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs.
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spelling pubmed-28003162010-01-01 Two Dosages of Oral Fluoropyrimidine S-1 of 35 and 40 mg/m(2) bid: Comparison of the Pharmacokinetic Profiles in Korean Patients with Advanced Gastric Cancer Jeung, Hei-Cheul Rha, Sun Young Shin, Sang Joon Ahn, Joong Bae Noh, Sung Hoon Roh, Jae Kyung Chung, Hyun Cheol Jpn J Clin Oncol Original Articles OBJECTIVE: In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after administration of S-1 at 35 or 40 mg/m(2) bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric cancer. METHODS: Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m(2), ranging from 70 to 88 mg/m(2). RESULTS: Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. C(max) and AUC(0–48 h) values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity. CONCLUSIONS: We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs. Oxford University Press 2010-01 2009-10-31 /pmc/articles/PMC2800316/ /pubmed/19880858 http://dx.doi.org/10.1093/jjco/hyp124 Text en © The Author (2009). Published by Oxford University Press http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Jeung, Hei-Cheul
Rha, Sun Young
Shin, Sang Joon
Ahn, Joong Bae
Noh, Sung Hoon
Roh, Jae Kyung
Chung, Hyun Cheol
Two Dosages of Oral Fluoropyrimidine S-1 of 35 and 40 mg/m(2) bid: Comparison of the Pharmacokinetic Profiles in Korean Patients with Advanced Gastric Cancer
title Two Dosages of Oral Fluoropyrimidine S-1 of 35 and 40 mg/m(2) bid: Comparison of the Pharmacokinetic Profiles in Korean Patients with Advanced Gastric Cancer
title_full Two Dosages of Oral Fluoropyrimidine S-1 of 35 and 40 mg/m(2) bid: Comparison of the Pharmacokinetic Profiles in Korean Patients with Advanced Gastric Cancer
title_fullStr Two Dosages of Oral Fluoropyrimidine S-1 of 35 and 40 mg/m(2) bid: Comparison of the Pharmacokinetic Profiles in Korean Patients with Advanced Gastric Cancer
title_full_unstemmed Two Dosages of Oral Fluoropyrimidine S-1 of 35 and 40 mg/m(2) bid: Comparison of the Pharmacokinetic Profiles in Korean Patients with Advanced Gastric Cancer
title_short Two Dosages of Oral Fluoropyrimidine S-1 of 35 and 40 mg/m(2) bid: Comparison of the Pharmacokinetic Profiles in Korean Patients with Advanced Gastric Cancer
title_sort two dosages of oral fluoropyrimidine s-1 of 35 and 40 mg/m(2) bid: comparison of the pharmacokinetic profiles in korean patients with advanced gastric cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800316/
https://www.ncbi.nlm.nih.gov/pubmed/19880858
http://dx.doi.org/10.1093/jjco/hyp124
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