长春瑞滨脂质体与长春瑞滨注射液在荷瘤小鼠体内的药代动力学及组织分布

Pharmacokinetics and biodistribution of vinorelbine-loaded liposomes and vinorelbine injection in tumor-bearing mice

采用S180荷瘤小鼠模型比较注射用长春瑞滨脂质体(L-NVB)与长春瑞滨注射液(NVB)在体内的药代动力学及其肺、骨髓、肿瘤组织中的分布差异。药代动力学研究显示L-NVB的AUC0-∞、cmax比市售NVB高,有提高药效的可能;而CLz降低,MRT延长,提示L-NVB可延长药物在体内的滞留时间,有助于增加扩散到肿瘤组织中的药物分布量;组织分布结果显示两种制剂在肺、骨髓、肿瘤组织中药物浓度变化趋势相似,L-NVB在骨组织的分布显著低于市售NVB(P﹤0.01),而在肿瘤组织的分布显著高于市售NVB(P﹤0.001),该结果提示L-NVB可通过滞留效应和延缓消除等双重因素在肿瘤组织中聚集,提高肿瘤组织中的靶向性,减少和缩短药物在毒性靶器官骨髓中的暴露量和暴露时间,从而降低骨髓毒性,提高疗效,满足临床用药需求。

S180 tumor-bearing mice were used to study the pharmaeokineties and biodistribution in lung, bone and tumor issues of vinorelbine-loaded liposome（L-NVB） and vinorelbine injection （NVB） in vivo. AUC0-∞ and Cmax of L-NVB higher than NVB, indicating its potential to improve theraputic effectiveness. While the decrease of CLz and the increase of MRT of L-NVB revealed that the liposomes could prolong the resistance time in blood and increase the drug amount that diffused into tumor tissues. Although the elimination tendency in lung, bone and tumor was similar, L-NVB displayed significantly decreased bone accumulation （P 〈 0.01） and significantly increased tumor accumulation （P 〈0. 001） compared with common NVB. These results demonstrated L-NVB could accumulate in tumor tissue due to enhanced permeability and retention effect, which improved the tumor targeting capability and reduced the drug dosage in other tissue such as bone. L-NVB showed better elinieal potential with reduced toxicity and improved theraputie effectiveness.