在区域热疗隔离肢体灌注期间，美法仑血浆药物水平存在显著差异。
Marked variability of melphalan plasma drug levels during regional hyperthermic isolated limb perfusion.
作者信息
Cheng Tsung-Yen, Grubbs Elizabeth, Abdul-Wahab Omar, Leu Szu-Yun, Hung Chen-Fang, Petros William, Aloia Thomas, Fedrau Randy, Pruitt Scott, Colvin Michael, Friedman Henry, Tyler Douglas
机构信息
Department of Surgery, Box 3118, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Am J Surg. 2003 Nov;186(5):460-7. doi: 10.1016/j.amjsurg.2003.07.019.
BACKGROUND
Hyperthermic isolated limb perfusion (HILP) with melphalan as treatment for locally recurrent or in-transit malignant melanoma is frequently performed but the principle for calculating drug dosage remains poorly understood.
METHODS
This study examined the pharmacokinetic profile of 14 consecutive patients to determine what variables were associated with toxicity and tumor responses.
RESULTS
Marked fourfold variability was noted in patient plasma melphalan concentrations. We defined a factor--the ratio of estimated limb volume (Vesti) to melphalan volume of distribution (Vss), Vesti/Vss--that was much more strongly correlated with acute regional toxicity than either area under concentration-time curve or peak plasma concentration. In addition, we found that AUX2 was the best correlate of tumor response.
CONCLUSIONS
Pharmacokinetic evaluation of prospective HILP trials is critical to not only understand response and toxicity outcomes but also to potentially improve the therapeutic index of regional perfusion.
背景
采用美法仑进行热灌注隔离肢体治疗局部复发性或转移性恶性黑色素瘤的操作十分常见，但药物剂量的计算原则仍鲜为人知。
方法
本研究检测了连续14例患者的药代动力学特征，以确定哪些变量与毒性和肿瘤反应相关。
结果
患者血浆中美法仑浓度存在显著的四倍差异。我们定义了一个因子——估计肢体体积（Vesti）与美法仑分布容积（Vss）的比值，即Vesti/Vss，该因子与急性局部毒性的相关性比浓度-时间曲线下面积或血浆峰浓度更强。此外，我们发现AUX2与肿瘤反应的相关性最佳。
结论
对前瞻性热灌注隔离肢体试验进行药代动力学评估不仅对于理解反应和毒性结果至关重要，而且对于潜在地提高区域灌注的治疗指数也很关键。
Zotero 插件