PMID: identifiant
de la référence Pubmed : |
 |
 (14650374)  |
|
| titre : |
|
Comparison of the pharmacokinetics of S-1, an oral anticancer agent, in Western and Japanese patients. |
|
| auteur(s) : |
|
Emmanuelle Comets ( ) 1, 2, Kazumasa Ikeda3, Paulo Hoff4, Pierre Fumoleau5, Jantien Wanders6, Yusuke Tanigawara1 |
|
| laboratoire : |
|
|
|
| résumé : |
|
OBJECTIVE: S-1 is an oral anticancer agent combining tegafur (FT), a prodrug of 5-fluorouracil (5-FU), with potassium oxonate (oteracil) and gimeracil (CDHP) respectively to mitigate gastrointestinal toxicity and increase the half-life of 5-FU. This article presents a population pharmacokinetic analysis of these four compounds in Western cancer patients. The second objective was to compare the pharmacokinetics of S-1 in Western and Japanese patients. METHODS: A single dose (25-45 mg/m2) of S-1 was administered to 60 patients. In each patient, 6 concentrations of FT, 5-FU, oteracil and CDHP were measured over 24 hr. Using NONMEM, oteracil and CDHP were analyzed separately, and the individual estimates of CDHP parameters were included in the joint analysis of FT and 5-FU. We used validation techniques to assess differences between the two populations, and finally we compared the exposures in Western and Japanese patients using simulations. RESULTS: A compartmental model describing the PK of the 4 compounds was developed. The influence of CDHP on the elimination of 5-FU was well described by an enzymatic inhibition model. The model provided a good fit for all compounds. The pharmacokinetics for 5-FU and oteracil were similar between Western and Japanese patients, but apparent differences in exposure to 5-FU resulted from different total doses due to different body sizes. |
|
| domaine : |
|
|
|
langue du texte
intégral : |
|
Anglais |
|
| ISSN : |
|
1567-567X |
|
|
| type de publication : |
|
Articles dans des revues avec comité de lecture |
|
| journal : |
|
| Journal of Pharmacokinetics and Pharmacodynamics (J Pharmacokinet Pharmacodyn) |
| Publisher |
Springer Verlag (Germany) |
| ISSN |
1567-567X (eISSN : 1573-8744) |
|
|
| Audience : |
|
internationale |
|
| date de publication : |
|
08/2003 |
|
| volume : |
|
30 |
|
| numéro : |
|
4 |
|
| page, identifiant, ... : |
|
257-83 |
|
|
| mots-clés auteur : |
|
5-FU – oral anticancer drug – population pharmacokinetics – model validation – ethnic differences |
|
| Descripteur(s) MeSH : |
|
Administration – Oral – Adult – Aged – Antimetabolites – Antineoplastic – Asian Continental Ancestry Group – Chi-Square Distribution – Clinical Trials – Drug Combinations – Europe – Female – Humans – Male – Middle Aged – Models – Biological – Oxonic Acid – Pyridines – Statistics – Nonparametric – Tegafur – United States – Western World |
|
| contrat, financement : |
|
During this work, Dr Emmanuelle Comets was supported by the fellowship program of the Japanese Society for the Promotion of Science |
|
