Pharmacokinetics and tissue distribution of novel traditional Chinese medicine-platinum anticancer agents in rats
Publication in refereed journal

香港中文大學研究人員

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摘要The pharmacokinetics and tissue distribution profiles of a novel series of traditional Chinese medicine-platinum (TCM-Pt) compounds [Pt(C8H8O5)(NH2R)(2)]: 1 (where R = H), 3 (R = CH3) and 5 (R = C6H10), were studied in Sprague-Dawley rats following a single bolus intravenous (i.v.) injection. Platinum concentrations in total plasma, plasma ultrafiltrate, urine and tissues were measured by flameless atomic absorption spectroscopy. Pharmacokinetic studies showed that plasma concentrations of total and free platinum for the novel TCM-Pt compounds as well as cisplatin and carboplatin declined in a biexponential manner with a short distribution half-life (t(1/2 alpha): 0.12-0.34 h). Compared with cisplatin, the novel TCM-Pt compounds had a longer elimination half-life (t(1/2 beta)), larger dose normalized area under the curve (AUC/D), larger volume of distribution at steady-state (V-ss), slower clearance (CL) of free platinum and higher percentage of cumulative urinary excretion (CUE), which can be attributed to their lower chemical reactivities. In tissues, the highest Pt concentrations were found in the kidney, followed by the liver and the lowest in the heart; no Pt was detected in the brain. Twenty-four hours after drug administration, platinum concentrations in tissues were significantly lower for the novel TCM-Pt compounds. These findings suggest that the novel compounds might afford higher clinical efficacy and reduced systemic side effects, when compared with cisplatin. (c) 2007 Elsevier Inc. All rights reserved.
著者Wang XN, Au-Yeung SCF, Ho YP
期刊名稱Journal of Inorganic Biochemistry
出版年份2007
月份6
日期1
卷號101
期次6
出版社ELSEVIER SCIENCE INC
頁次909 - 917
國際標準期刊號0162-0134
語言英式英語
關鍵詞carboplatin; cisplatin; pharmacokinetics; protein binding; TCM-Pt compounds; tissue distribution
Web of Science 學科類別Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Chemistry; Chemistry, Inorganic & Nuclear; CHEMISTRY, INORGANIC & NUCLEAR

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