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Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer

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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.

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Acknowledgments

This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare (A020436) and in part by a grant from Sanofi-Synthelabo Korea, Republic of Korea. Technical support by SK Chemicals for platinum analysis was greatly appreciated.

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Authors and Affiliations

  1. Catholic Research Institutes of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, 137-701, Seoul, Korea

    Jung-Won Lee, Jong-Kook Park, Jin-Hyoung Kang, Kyung-Shik Lee & Hyo-Jeong Kuh

  2. Medical and Regulatory Affairs, Schering Korea, Seoul, Korea

    Hea-Kyoung Cho

  3. Seoul National University Bundang Hospital, Gyeonggi, Korea

    Eun-Sook Lee

  4. College of Pharmacy, Seoul National University, Seoul, Korea

    Chang-Koo Shim, Suk-Jae Chung & Dae-Duk Kim

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  1. Hea-Kyoung Cho
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Correspondence to Hyo-Jeong Kuh.

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Cho, HK., Lee, ES., Lee, JW. et al. Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer. J Cancer Res Clin Oncol 132, 320–326 (2006). https://doi.org/10.1007/s00432-005-0072-6

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  • DOI: https://doi.org/10.1007/s00432-005-0072-6

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