Pharmacokinetics and tissue distribution of iv injection of polyphase liposome-encapsulated cisplatin (KM-1) in rats.
OBJECTIVE
The pharmacokinetics and biodistribution of cisplatin encapsulated in polyphase liposome (KM-1) were compared with those of free drug in rats.


METHODS
The platinum levels in serum and normal organs, after a single dose of iv injection of free or encapsulated cisplatin to rats, were determined by induced coupled plasma atomic emission spectrometry.


RESULTS
Serum platinum concentration-time curve after a single iv dose of KM-1 4.5 mg/kg in rats was fitted with an open three-compartment model. The pharmacokinetic parameters were as follows: Vc=0.10 L/kg, T1/2pai=0.3 h, T1/2alpha=3.5 h, T1/2beta=2.7 h, AUC=265 mg.h.L(-1), and CL(s) =0.02 g.L.h(-1). KM-1 was cleared from the circulation much more slowly than free cisplatin. Liver and spleen had the highest concentration of platinum after KM-1 treatment.


CONCLUSIONS
KM-1 remained in the bloodstream longer than its free drug, and was taken mainly by the reticuloendothelial system.
Wang
Shan
S
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. wangshan420@163.net
Mi
Jie-Bo
JB
Li
Yuan-Zong
YZ
Chang
Wen-Bao
WB
Ci
Yun-Xiang
YX
Zhao
Min-Zheng
MZ
Zhao
Yun-Kun
YK
Zhu
Li-Ya
LY
Xu
Guang
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers; D007275:Injections, Intravenous; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008297:Male; D010984:Platinum / Q000032:analysis / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010984:Platinum; D002945:Cisplatin