Jehn C F, Boulikas T, Kourvetaris A, Possinger K, Lüftner D
Medizinische Klinik und Poliklinik mit Schwerpunkt Onkologie und Hämatologie Charité, Campus Mitte, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin Charitéplatz 1, 10117 Berlin, Germany.
Anticancer Res. 2007 Jan-Feb;27(1A):471-5.
Lipoplatin, a novel liposomal formulation of cisplatin, is composed of cisplatin and liposomes based on dipalmityl phosphatidyl glycerol (DPPG), soy phosphatidyl choline (SPC-3), cholesterol and methoxypolyethylene glycol-distearoyl phosphatidylethanolamine (mPEG2000-DSPE). Liposomal encapsulation of cisplatin is designed to increase safety and tolerability by decreasing, e.g., nephrotoxicity through decreased exposure of organs to cisplatin, while effectively delivering the drug to the tumor. In an ongoing phase III trial comparing cisplatin to lipoplatin (both in combination with infusional high-dose 5-Fluoruracil) in advanced head and neck cancer (HNC), a sub-study to determine the pharmacokinetic profile of lipoplatin in comparison to conventional cisplatin was undertaken.
In total, twelve patients with advanced HNC received a combination chemotherapy with either lipoplatin/5-FU or cisplatin/5-FU. Plasma samples were analyzed for concentration of total platinum in patients from both arms.
All twelve patients from the pharmacokinetic sub-study were male Caucasians at a mean age of 60 years. There was no difference in age or kidney function between the two treatment groups. The total body clearance for cisplatin was 1.25 L/(hxm2) for the liposomal formulation, compared to 0.62 L/(hxm2) for conventional cisplatin. The terminal half life was half as long for lipoplatin (10.98 h) as compared to cisplatin (24.5h). Even though the maximum observed concentration in the plasma (C(max) was greater for lipoplatin than for cisplatin, the area under the concentration time-curve (AUC) was less (6.5 microg/ml vs. 4.07 microg/ml and 66.85 microg/h/ml vs. 130.33 microg/h/ml, respectively).
The pharmacokinetic profile of lipoplatin (in combination with 5-FU) suggests that the liposomal formulation results in a greater body clearance and shorter half life than conventional cisplatin, which confirms the clinical observation of decreased taxicity, especially renal deterioration.
脂铂是一种新型的顺铂脂质体制剂，由顺铂和基于二棕榈酰磷脂酰甘油（DPPG）、大豆卵磷脂（SPC - 3）、胆固醇和甲氧基聚乙二醇 - 二硬脂酰磷脂酰乙醇胺（mPEG2000 - DSPE）的脂质体组成。顺铂的脂质体包封旨在通过减少器官对顺铂的暴露等方式提高安全性和耐受性，例如降低肾毒性，同时有效地将药物递送至肿瘤部位。在一项正在进行的III期试验中，将顺铂与脂铂（两者均与静脉输注高剂量5 - 氟尿嘧啶联合使用）用于晚期头颈癌（HNC）的治疗，同时开展了一项子研究以确定脂铂与传统顺铂相比的药代动力学特征。
总共12例晚期HNC患者接受了脂铂/5 - FU或顺铂/5 - FU联合化疗。对两组患者的血浆样本进行总铂浓度分析。
药代动力学子研究中的所有12例患者均为男性白种人，平均年龄60岁。两个治疗组在年龄或肾功能方面无差异。脂质体制剂的顺铂全身清除率为1.25 L/（h·m²），而传统顺铂为0.62 L/（h·m²）。脂铂的终末半衰期（10.98小时）是顺铂（24.5小时）的一半。尽管血浆中观察到的最大浓度（Cmax）脂铂高于顺铂，但浓度 - 时间曲线下面积（AUC）较小（分别为6.5μg/ml对4.07μg/ml以及66.85μg/h/ml对130.33μg/h/ml）。
脂铂（与5 - FU联合使用）的药代动力学特征表明，脂质体制剂比传统顺铂具有更高的全身清除率和更短的半衰期，这证实了毒性降低尤其是肾脏损害减轻的临床观察结果。
