Didolkar M S, Jackson A J, Lesko L J, Fitzpatrick J L, Buda B S, Johnston G S, Zech L A
Department of Surgery, Sinai Hospital, Baltimore, MD 21215, USA.
J Surg Oncol. 1996 Nov;63(3):148-58. doi: 10.1002/(SICI)1096-9098(199611)63:3<148::AID-JSO4>3.0.CO;2-D.
The pharmacokinetics of dacarbazine (DTIC), which has been shown to be an effective therapeutic agent against metastatic melanoma, has not been extensively studied. However, to improve the clinical use of the drug, more information on the kinetics is required.
A pharmacokinetic study was undertaken in six patients with melanoma of an extremity who were undergoing hyperthermic isolation perfusion with DTIC in order to understand better its clinical pharmacokinetics. Plasma was sampled from the arterial and venous lines of an extracorporeal pump during the perfusion with the systemic vein and urine sampled postperfusion. Samples were analyzed for DTIC. 2-azahypoxanthine (2-AZA), and aminoimidazole carboxamide (AIC). 99(m)Tc (Technetium) human serum albumin (HSA) was used in the perfusion circuit to monitor the crossover of the perfusate into the systemic circulation during the procedure. The data were analyzed using a compartmental model of sampled body compartments incorporating the isolated extremity.
High tissue DTIC levels were maintained throughout the perfusion, whereas in the systemic circulation, plasma DTIC concentrations, when observed, were 40-100-fold less than those in the perfusate. Almost 70% of the DTIC administered was not recovered in the perfusate after the washout of the extremity.
High levels of DTIC can be maintained in an extremity (i.e., arm or leg) during perfusion.
达卡巴嗪（DTIC）已被证明是一种治疗转移性黑色素瘤的有效药物，但其药代动力学尚未得到广泛研究。然而，为了改善该药物的临床应用，需要更多关于其动力学的信息。
对6例肢体黑色素瘤患者进行了一项药代动力学研究，这些患者正在接受DTIC热隔离灌注，以便更好地了解其临床药代动力学。在通过体循环静脉进行灌注期间，从体外泵的动脉和静脉管路采集血浆，并在灌注后采集尿液。对样本进行DTIC、2-氮杂次黄嘌呤（2-AZA）和氨基咪唑甲酰胺（AIC）分析。在灌注回路中使用99（m）锝（Tc）人血清白蛋白（HSA）来监测灌注液在手术过程中进入体循环的情况。使用包含隔离肢体的采样身体隔室的房室模型对数据进行分析。
在整个灌注过程中，组织中的DTIC水平保持较高，而在体循环中，观察到的血浆DTIC浓度比灌注液中的浓度低40-100倍。在肢体冲洗后，灌注液中未回收近70%给予的DTIC。
在灌注过程中，DTIC可以在肢体（即手臂或腿部）中维持高浓度。
