title: Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer.
abstract: 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.
authors.affiliation: Medical and Regulatory Affairs, Schering Korea, Seoul, Korea.
authors.forename: Hea-Kyoung
authors.initials: HK
authors.lastname: Cho
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Jong-Kook
authors.initials: JK
authors.lastname: Park
authors.forename: Jin-Hyoung
authors.initials: JH
authors.lastname: Kang
authors.forename: Kyung-Shik
authors.initials: KS
authors.lastname: Lee
authors.forename: Chang-Koo
authors.initials: CK
authors.lastname: Shim
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Kuh
mesh_terms: 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
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum; D003404:Creatinine; D002955:Leucovorin; D005472:Fluorouracil