Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer.
OBJECTIVE
Oxaliplatin and 5-fluorouracil (5-FU) act synergistically in colorectal cancer. Here, we evaluated the pharmacokinetics of oxaliplatin and 5-FU administered in combination with leucovorin in Korean advanced colorectal cancer patients.


METHODS
Nine patients with advanced colorectal cancer were included in this study. The 3-week regimen consisted of oxaliplatin (2-h infusion, 130 mg/m(2)on day 1) followed by 5-FU and leucovorin (2-h infusion, 425 and 20 mg/m(2), respectively, from day 1 to day 5). Blood samples were taken and platinum concentrations in total plasma, plasma ultrafiltrate, and RBCs were determined. Plasma concentrations of 5-FU were also determined.


RESULTS
The C (max) of oxaliplatin was observed at the end of infusion, with mean values of 4.66, 0.84, and 2.69 microg/ml for total plasma, plasma ultrafiltrate, and RBC samples, respectively. C (max) ratios of total/free were significantly higher than those reported in other ethnic groups. An accumulation of platinum was observed in RBCs, but not in total plasma and plasma ultrafiltrate samples. A significant correlation was found between the total body clearance of ultrafiltrable platinum and creatinine clearance. The C (max) of plasma 5-FU ranged from 23.9 to 533.8 ng/ml, indicating large inter-patient pharmacokinetic variations.


CONCLUSIONS
This study shows that pharmacokinetics of oxaliplatin in Korean patients is comparable with that of other ethic groups, except for the higher C (max) ratios of total/free. The C (max) of 5-FU in plasma showed large variations among patients. Antitumor efficacy in Korean advanced colorectal cancer patients given oxaliplatin and 5-FU should be further evaluated with respect to pharmacokinetic variabilities.
Cho
Hea-Kyoung
HK
Medical and Regulatory Affairs, Schering Korea, Seoul, Korea.
Lee
Eun-Sook
ES
Lee
Jung-Won
JW
Park
Jong-Kook
JK
Kang
Jin-Hyoung
JH
Lee
Kyung-Shik
KS
Shim
Chang-Koo
CK
Chung
Suk-Jae
SJ
Kim
Dae-Duk
DD
Kuh
Hyo-Jeong
HJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007723:Korea; D002955:Leucovorin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077150:Oxaliplatin; D010984:Platinum / Q000032:analysis
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum; D003404:Creatinine; D002955:Leucovorin; D005472:Fluorouracil