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Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients
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Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients
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Journal Article
Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients
2011
Overview
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/m2 b.i.d. for 14 days every 21 days. Dose normalized AUC0–48 h for tegafur (P = 0.05) and gimeracil (P = 0.036) were higher in East Asians; conversely, AUC0–48 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. (Cancer Sci 2011; 102: 478–483)
Publisher
Blackwell Publishing Ltd,Blackwell
Subject
/ Aged
/ Antimetabolites, Antineoplastic - adverse effects
/ Antimetabolites, Antineoplastic - pharmacokinetics
/ Aryl Hydrocarbon Hydroxylases - genetics
/ Asian Continental Ancestry Group - genetics
/ Biological and medical sciences
/ European Continental Ancestry Group - genetics
/ Far East
/ Female
/ Genotype
/ Humans
/ Male
/ Oxonic Acid - adverse effects
/ Oxonic Acid - pharmacokinetics
/ Tumors
