title: Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients.
abstract: S-1 is an oral fluoropyrimidine anti-neoplastic agent that is converted by CYP2A6 to 5-fluorouracil (5FU). We prospectively studied the pharmacokinetics and pharmacodynamics of S-1 in two groups of East Asian and Caucasian patients with solid malignancy refractory to standard chemotherapy, or for which 5FU was indicated, to elucidate differences in relation to CYP2A6 genotype and phenotype. S-1 was given orally at 30 mg/m(2) b.i.d. for 14 days every 21 days. Dose normalized AUC(0-48 h) for tegafur (P = 0.05) and gimeracil (P = 0.036) were higher in East Asians; conversely, AUC(0-48 h) of fluoro-β-alanine was higher in Caucasians (P = 0.044). Exposure to 5FU was similar in both groups (P = 0.967). Mean cotinine:nicotine ratio was 54% higher in the Caucasian group (P = 0.03), and correlated with oral clearance of tegafur (r = 0.59; P = 0.002). Grade 3/4 gastrointestinal toxicities were more common in Caucasians than Asians (21%vs 0%). Treatment with S-1 yields no significant difference in 5FU exposure between Caucasians and East Asians.
authors.affiliation: Department of Hematology-Oncology, National University Health System, Cancer Sciences Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chuah
authors.forename: Boon-Cher
authors.initials: BC
authors.lastname: Goh
authors.forename: Soo-Chin
authors.initials: SC
authors.lastname: Lee
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
authors.forename: Fayce
authors.initials: F
authors.lastname: Lau
authors.forename: Marilyn
authors.initials: M
authors.lastname: Mulay
authors.forename: Melissa
authors.initials: M
authors.lastname: Dinolfo
authors.forename: Siew-Eng
authors.initials: SE
authors.lastname: Lim
authors.forename: Ross
authors.initials: R
authors.lastname: Soo
authors.forename: Taro
authors.initials: T
authors.lastname: Furuie
authors.forename: Kaku
authors.initials: K
authors.lastname: Saito
authors.forename: Christopher
authors.initials: C
authors.lastname: Zergebel
authors.forename: Lee S
authors.initials: LS
authors.lastname: Rosen
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics; D065637:Cytochrome P-450 CYP2A6; D004338:Drug Combinations; D005202:Asia, Eastern; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D010094:Oxonic Acid / Q000009:adverse effects / Q000493:pharmacokinetics*; D010641:Phenotype; D005641:Tegafur / Q000009:adverse effects / Q000493:pharmacokinetics*; D044465:White People / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6