Hea-Kyoung Cho2, Eun-Sook Lee3, Jung-Won Lee1, Jong-Kook Park1, Jin-Hyoung Kang1, Kyung-Shik Lee1, Chang-Koo Shim4, Suk-Jae Chung4, Dae-Duk Kim4 and Hyo-Jeong Kuh1
(1) Catholic Research Institutes of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, 137-701 Seoul, Korea
(2) Medical and Regulatory Affairs, Schering Korea, Seoul, Korea
(3) Seoul National University Bundang Hospital, Gyeonggi, Korea
(4) College of Pharmacy, Seoul National University, Seoul, Korea
Received: 18 October 2005 Accepted: 8 December 2005 Published online: 4 January 2006
Abstract Purpose: 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/m2 on day 1) followed by 5-FU and leucovorin (2-h infusion, 425 and 20 mg/m2, 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 μg/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.
Keywords Oxaliplatin - 5-Fluorouracil - Pharmacokinetics - Colorectal cancer
Subscribe to:
Post Comments (Atom)
No comments:
Post a Comment