Effects of a low-fat meal on the oral bioavailability of UFT and leucovorin in patients with colorectal cancer.
BACKGROUND
UFT is composed of tegafur, a prodrug of 5-fluorouracil, and uracil, at a fixed ratio of 1: 4. UFT is widely used with leucovorin as adjuvant chemotherapy in patients with colon cancer. As reported, UFT/leucovorin should not be taken simultaneously with food because a high fat content will reduce the systemic exposure to the active cytotoxic moiety of UFT. In this single-dose, randomized, two-way crossover study, we investigated the effects of a low-fat Japanese meal on the pharmacokinetics and oral bioavailability of UFT (2 x 100-mg capsules; dose in terms of tegafur) and leucovorin (1 x 25-mg tablet).


METHODS
Patients (n = 12) were randomly assigned to receive both drugs after an overnight fast or 5 min after eating a standard Japanese breakfast (641 kcal), with a 3-day washout period between treatments. Pharmacokinetics (n = 12) were determined for tegafur, 5-fluorouracil, uracil, leucovorin, and 5-methyltetrahydrofolate (an active metabolite of leucovorin).


RESULTS
For 5-fluorouracil pharmacokinetics, the maximum plasma concentration and the area under the curve were reduced by 73.7% and 47.4%, respectively, when UFT was taken postprandially, and the maximum plasma concentration and the area under the curve for uracil were reduced by 84.1% and 68.9%, respectively, compared with dosing on an empty stomach. These decreases in the systemic exposure to 5-fluorouracil were quite marked and may have an impact on its antitumor effect.


CONCLUSIONS
A low-fat meal affects the pharmacokinetics of UFT similarly to a high-fat meal.
Furuhata
Tomohisa
T
First Department of Surgery, Sapporo Medical University, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan. furuhata@sapmed.ac.jp
Meguro
Makoto
M
Nishidate
Toshihiko
T
Okita
Kenji
K
Ishiyama
Gentarou
G
Iwayama
Yuuji
Y
Hosokawa
Yuuichi
Y
Tsuruma
Tetsuhiko
T
Kimura
Yasutoshi
Y
Mizuguchi
Toru
T
Sasaki
Kazuaki
K
D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018752:Diet, Fat-Restricted; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics; D014498:Uracil / Q000008:administration & dosage / Q000493:pharmacokinetics
D011355:Prodrugs; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin