Pharmacokinetic and pharmacodynamic studies with 4′-epi-doxorubicin in nasopharyngeal carcinoma patients

Oliver Yoa Pu Hu, Shiu Pei Chang, Jer Min Jame, Kuang Yao Chen

研究成果: 雜誌貢獻文章同行評審

25 引文 斯高帕斯(Scopus)

摘要

The plasma pharmacokinetic profile of 4′-epidoxorubicin (epirubicin) was investigated in 28 patients with nasopharyngeal carcinoma (NPC) after single i.v. rapid infusions. All patients had normal liver and renal functions. Plasma concentrations of the parent compound were specifically determined by a high-performance liquid chromatographic (HPLC) method, with UV detection at 254 nm. Plasma levels of the compound were fitted to a three-compartment open model; a triexponential decrease in plasma concentrations with a long terminal plasma halflife (44.8±21.2 h) was observed in 27 patients. The respective mean (±SD) serum concentration at 72 h and the AUC, plasma clearance, and terminal elimination rate constant in complete responders were 7.67±1.98 ng/ml, 4,002±3,080 ng· h/ml, 26.6±12.9 l/h·m2, and 0.009±0.007 l/h, whereas those in nonresponders were 4.96±1.8 ng/ml, 1,88±652.8 ng·h/ml, 44.4±15 l/h·m2, and 0.017±0.006 l/h, respectively; these differences were significant (P(0.05). Epirubicin produced a 52% response rate, including 6 patients with a complete response, 8 with a partial response, 11 with no change, and 2 with progressive disease. No relationship could be found between the various pharmacokinetic parameters and either leukopenia, age, or sex. These observations strongly suggest that plasma clearance may be one of the determining factors affecting the response or nonresponse of NPC patients to epirubicin, and a dose adjustment according to plasma clearance would probably increase the response rate.
原文英語
頁(從 - 到)332-337
頁數6
期刊Cancer Chemotherapy and Pharmacology
24
發行號5
DOIs
出版狀態已發佈 - 十月 1 1989
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 毒理學
  • 藥理
  • 癌症研究
  • 藥學(醫學)

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