Pharmacokinetic study of S-1 in patients in whom inulin clearance was measured.
OBJECTIVE
This pharmacokinetic study of S-1 was conducted in patients in whom glomerular filtration rate (GFR) was directly measured to explore the possibility of adjusting the S-1 dose on the basis of GFR in patients with normal or nearly normal renal function.


METHODS
S-1 was given to 12 patients twice daily for 28 consecutive days followed by 14 days of rest, repeated every 6 weeks. GFR was measured on the basis of inulin clearance (CLin) before the first day of treatment.


RESULTS
The area under the time-concentration curve (AUC) of 5-fluorouracil (5-FU) correlated with that of 5-chloro-2,4-dihydroxypyridine (CDHP, r = 0.750, p = 0.005). The AUC of CDHP correlated with the measured 24-hour creatinine clearance (CLcr) per subject (r = -0.620, p = 0.032), but not with the CLin (r = -0.356, p = 0.257). The AUC of 5-FU did not correlate with either the 24-hour CLcr per subject (r = -0.401, p = 0.187) or with the CLin (r = -0.300, p = 0.351).


CONCLUSIONS
Dosage adjustment based on the GFR does not reduce individual variations in 5-FU concentrations among patients with normal or nearly normal renal function who receive S-1.
Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi, Japan.
Yuichi
Y
Ando
Kenji
K
Kawada
Megumi
M
Inada
Sachi
S
Morita
Ayako
A
Mitsuma
Yoshinari
Y
Yasuda
Mariko
M
Hiramatsu
Yasushi
Y
Fujimoto
Ken-ichi
K
Fujita
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003404:Creatinine / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate; D006801:Humans; D007444:Inulin / Q000493:pharmacokinetics*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011725:Pyridines / Q000493:pharmacokinetics; D012016:Reference Values; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D007444:Inulin; D003404:Creatinine; D005472:Fluorouracil; C104201:gimeracil