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阿霉素及其主要代谢产物阿霉素醇的药代动力学新数据。

New data on the pharmacokinetics of adriamycin and its major metabolite, adriamycinol.

作者信息

Leca F, Marchiset-Leca D, Noble A, Antonetti M

机构信息

Laboratoire de Pharmacocinétique, C.H.D. Castelluccio, Ajaccio, France.

出版信息

Eur J Drug Metab Pharmacokinet. 1991 Apr-Jun;16(2):107-11. doi: 10.1007/BF03189946.

Abstract

Twenty-two days after administration by intravenous bolus, of 50 mg of adriamycin to several patients we found concentrations of adriamycin and adriamycinol of the order of 100 pcg/ml. In theory, however, with a terminal half-life of 30 h, the plasma levels of adriamycin and adriamycinol should be close to 0.1 pcg/ml. Further pharmacokinetic investigation was therefore necessary. We have retained for this study nine male patients, aged between 53 and 69 years who received 25 to 50 mg of adriamycin by slow intravenous injection. The HPLC method permitted the detection of 50 pcg/ml of adriamycin and adriamycinol, with the possibility of monitoring their elimination during 120 h (and in one case during 160 h). The terminal half-lives of elimination estimated in 8 patients were respectively 110 +/- 52 h for adriamycin and 92 h 50 min +/- 43 h for adriamycinol. Surface ratios under adriamycinol curves against calculated adriamycin was 1.10 +/- 0.26. Plasma levels found during the To in certain patients correspond to the end of the drug elimination of the previous treatment. It is difficult with a half-life to 110 h to predict the effects of residual concentrations of adriamycin and adriamycinol.

摘要

在对几名患者静脉推注50毫克阿霉素22天后,我们发现阿霉素和阿霉素醇的浓度约为100微克/毫升。然而,理论上,阿霉素的终末半衰期为30小时,其血浆水平应接近0.1微克/毫升。因此,有必要进行进一步的药代动力学研究。我们选取了9名年龄在53至69岁之间的男性患者进行本研究,这些患者通过缓慢静脉注射接受了25至50毫克的阿霉素。高效液相色谱法能够检测到50微克/毫升的阿霉素和阿霉素醇,并有可能监测它们在120小时(其中1例为160小时)内的消除情况。在8名患者中估计的阿霉素和阿霉素醇的终末消除半衰期分别为110±52小时和92小时50分钟±43小时。阿霉素醇曲线下面积与计算出的阿霉素面积之比为1.10±0.26。在某些患者的给药间隔期(T₀)发现的血浆水平对应于先前治疗药物消除的末期。对于半衰期为110小时的情况,很难预测阿霉素和阿霉素醇残留浓度的影响。

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