Pharmacokinetic and pharmacodynamic studies with mitoxantrone in the treatment of patients with nasopharyngeal carcinoma

Oliver Yoa‐Pu Hu, Shiu‐Pei ‐P Chang, Chi‐Kong ‐K Law, Jer‐Min ‐M Jian, Kuang‐Yao ‐Y Chen

研究成果: 雜誌貢獻文章同行評審

19 引文 斯高帕斯(Scopus)

摘要

The pharmacokinetics and pharmacodynamics of mitoxantrone were studied in 15 patients with advanced nasopharyngeal carcinoma (NPC) after single intravenous rapid infusion (12 to 14 mg/m2). Mitoxantrone plasma concentrations and urinary excretion were measured specifically with the use of a high‐performance liquid chromatographic method with ultraviolet detection at 242 and 658 nm. The pharmacokinetic parameters are described adequately by a three‐compartment model with a terminal half‐life of 71.5 ± 40.1 hours and a volume of distribution of 5037 ± 2377 l0. The total plasma clearance was 743 ± 462 ml/minute, and the renal clearance was 18.8 ± 8.49 ml/minute. Within 72 hours, 1.8 ± 0.6% of the administration dose was excreted in urine as mitoxantrone parent compound. From the urinary excretion rate data, glomerular filtration and possible tubular reabsorption were the mechanisms involved in the urinary excretion of mitoxantrone. The values for unbound fraction (%) in plasma at time 0 and 5 minutes were 2.88 ± 0.91% and 3.25 ± 1.19%, with an average of 3.04 ± 1.01%. The degree of protein binding of mitoxantrone was not affected by concentration (P > 0.05) in Chinese patients with NPC. The response rate for mitoxantrone was poor in this study. Clinical studies have demonstrated that mitoxantrone was generally well tolerated. Only very low incidences of nausea, vomiting, and alopecia were observed. The mild and rapidly reversible dose‐limiting hematologic toxic effects have proven leukopenia. Although the toxicities reported here were tolerated for most patients, other combination regimens including mitoxantrone or other administration routes may be considered and need to be evaluated carefully. Cancer 1992; 69:847–853.
原文英語
頁(從 - 到)847-853
頁數7
期刊Cancer
69
發行號4
DOIs
出版狀態已發佈 - 一月 1 1992
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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