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米托蒽醌在人体内的药代动力学和代谢

The pharmacokinetics and metabolism of mitoxantrone in man.

作者信息

Ehninger G, Proksch B, Heinzel G, Schiller E, Weible K H, Woodward D L

出版信息

Invest New Drugs. 1985;3(2):109-16. doi: 10.1007/BF00174157.

DOI:10.1007/BF00174157
PMID:4019115
Abstract

An HPLC method using paired-ion chromatography on RP C-18 material was developed. After sample clean up on XAD columns, mitoxantrone (Novantrone; dihydroxyanthracenedione) in concentrations below 1 ng/ml in serum and 0.2 ng/ml in urine were measurable with a coefficient of variation less than 9.3% at a wavelength of 658 nm. Four metabolites were separated in urine. The major metabolite cochromatographed with the synthesized dicarboxylic acid of mitoxantrone. Within 48 hours 4.4% of the administered dose was excreted in urine as mitoxantrone, 0.5% as metabolite 1 and 0.3% as metabolite 2. The pharmacokinetic parameters are adequately described by a three-compartment model with a terminal half-life of 214.8 hours, and a volume of distribution (ss) of 3792 litres. The total body clearance was 358 ml/min and the renal clearance was 26.2 ml/min.

摘要

开发了一种在RP C-18材料上使用配对离子色谱法的高效液相色谱法。在XAD柱上对样品进行净化后,在658nm波长下,血清中浓度低于1ng/ml、尿液中浓度低于0.2ng/ml的米托蒽醌(诺维本;二羟基蒽二酮)可被检测到,变异系数小于9.3%。在尿液中分离出了四种代谢物。主要代谢物与合成的米托蒽醌二羧酸共色谱。在48小时内,给药剂量的4.4%以米托蒽醌形式经尿液排出,0.5%以代谢物1形式排出,0.3%以代谢物2形式排出。药代动力学参数可用三室模型充分描述,终末半衰期为214.8小时,分布容积(稳态)为3792升。总体清除率为358ml/min,肾清除率为26.2ml/min。

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1
The pharmacokinetics and metabolism of mitoxantrone in man.米托蒽醌在人体内的药代动力学和代谢
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2
Detection and separation of mitoxantrone and its metabolites in plasma and urine by high-performance liquid chromatography.高效液相色谱法检测和分离血浆及尿液中的米托蒽醌及其代谢产物
J Chromatogr. 1985 Jul 12;342(1):119-27. doi: 10.1016/s0378-4347(00)84494-1.
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本文引用的文献

1
Clinical analysis for the anti-neoplastic agent 1,4-dihydroxy-5,8-bis((2-[(2-hydroxyethyl)amino]ethyl)-amino)9,10-anthracenedio ne dihydrochloride (NSC 301739) in plasma. Application of temperature control to provide selectivity in paired-ion high-performance liquid chromatography.血浆中抗肿瘤药物1,4 - 二羟基 - 5,8 - 双((2 - [(2 - 羟乙基)氨基]乙基)氨基)-9,10 - 蒽二酮二盐酸盐(NSC 301739)的临床分析。温度控制在离子对高效液相色谱中提供选择性的应用。
J Chromatogr. 1981 Feb 13;222(2):225-40.
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Improved high-performance liquid chromatography of the new antineoplastic agents bisantrene and mitoxantrone.新型抗肿瘤药物双胺苯吖啶和米托蒽醌的高效液相色谱法改进
J Chromatogr. 1982 Dec 10;233:235-47. doi: 10.1016/s0378-4347(00)81750-8.
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Mitoxantrone: a review of its use in multiple sclerosis.
米托蒽醌:其在多发性硬化症中的应用综述
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Mitoxantrone. A review of its pharmacology and clinical efficacy in the management of hormone-resistant advanced prostate cancer.米托蒽醌。其在激素抵抗性晚期前列腺癌治疗中的药理学及临床疗效综述。
Drugs Aging. 1997 Jun;10(6):473-85. doi: 10.2165/00002512-199710060-00007.
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Mitoxantrone: a review of its pharmacological properties and use in acute nonlymphoblastic leukaemia.米托蒽醌:其药理特性及在急性非淋巴细胞白血病中的应用综述
Drugs Aging. 1996 Aug;9(2):122-47. doi: 10.2165/00002512-199609020-00007.
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Poly(I).poly(C), a potential drug carrier for the antitumor agent mitoxantrone: in vitro drug binding study.聚肌苷酸-聚胞苷酸,一种用于抗肿瘤药物米托蒽醌的潜在药物载体:体外药物结合研究
Cancer Chemother Pharmacol. 1987;20(1):81-2. doi: 10.1007/BF00252966.
7
Comparative in vitro toxicity of mitoxantrone and adriamycin in human granulocyte-macrophage progenitor cells.米托蒽醌与阿霉素对人粒细胞-巨噬细胞祖细胞的体外毒性比较
Cancer Chemother Pharmacol. 1987;20(1):8-12. doi: 10.1007/BF00252951.
8
Human central nervous system and plasma pharmacology of mitoxantrone.米托蒽醌的人体中枢神经系统和血浆药理学
J Neurooncol. 1988;6(1):75-83. doi: 10.1007/BF00163544.
9
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Eur J Drug Metab Pharmacokinet. 1990 Jul-Sep;15(3):219-22. doi: 10.1007/BF03190207.
10
Pharmacokinetics and metabolism of mitoxantrone. A review.
Clin Pharmacokinet. 1990 May;18(5):365-80. doi: 10.2165/00003088-199018050-00003.
Clinical and clinical pharmacologic studies of mitoxantrone.
Cancer Treat Rep. 1982 Jun;66(6):1327-31.
4
Clinical kinetics of 1, 4-dihydroxy-5,8-bis [(2-[(2-hydroxyethyl) amino] ethyl] amino ]-9, 10-anthracenedione.1,4 - 二羟基 - 5,8 - 双[(2 - [(2 - 羟乙基)氨基]乙基]氨基] - 9,10 - 蒽二酮的临床动力学
Clin Pharmacol Ther. 1982 Mar;31(3):312-6. doi: 10.1038/clpt.1982.39.
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Cancer Res. 1983 Aug;43(8):3919-22.
6
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