Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer.
BACKGROUND
The combination of gemcitabine (GEM) and S-1, an oral 5-fluorouracil (5-FU) derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer.


METHODS
Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK) study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed.


RESULTS
The maximum concentration (Cmax), the area under the curve from the drug administration to the infinite time (AUCinf), and the elimination half-life (T1/2) of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax) were not significantly different between S-1 administration with and without GEM.


CONCLUSIONS
There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.
Nakata
Bunzo
B
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan. bunzo@med.osaka-cu.ac.jp
Amano
Ryosuke
R
Nakao
Shigetomi
S
Tamura
Tatsuro
T
Shinto
Osamu
O
Hirakawa
Toshiki
T
Okita
Yoshihiro
Y
Yamada
Nobuya
N
Hirakawa
Kosei
K
D000284:Administration, Oral; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000097:blood* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D004338:Drug Combinations; D004347:Drug Interactions; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000097:blood*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000097:blood*; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000188:drug therapy; D005641:Tegafur / Q000008:administration & dosage / Q000097:blood*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil; D000093542:Gemcitabine