Pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone hydrochloride.
- Author:
Cai-xia WANG
1
;
Chun-lei LI
;
Xi ZHAO
;
Han-yu YANG
;
Na WEI
;
Yan-hui LI
;
Li ZHANG
;
Lan ZHANG
Author Information
1. Hebei Pharmaceutical Technology and Engineering Research Center, Shijiazhuang 050051, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antineoplastic Agents;
administration & dosage;
pharmacokinetics;
pharmacology;
Area Under Curve;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Dogs;
Dose-Response Relationship, Drug;
Drug Carriers;
Female;
Humans;
Injections, Intravenous;
Liposomes;
chemistry;
Male;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Mitoxantrone;
administration & dosage;
pharmacokinetics;
pharmacology;
Neoplasm Transplantation;
Prostatic Neoplasms;
pathology;
Sarcoma 180;
pathology;
Tissue Distribution
- From:
Acta Pharmaceutica Sinica
2010;45(12):1565-1569
- CountryChina
- Language:Chinese
-
Abstract:
This study is to compare the pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone (Mit-lipo) and free mitoxantrone (Mit-free). The antineoplastic effect of Mit-lipo was evaluated on PC-3 human xenograft tumor model after repeated intravenous injection at dose levels of 1, 2 and 4 mg x kg(-1). The pharmacokinetic study of Mit-lipo and Mit-free was performed on dogs following a single intravenous injection. The tissue distribution of Mit-lipo and Mit-free was observed on S-180 bearing mice after a single intravenous injection. (1) Pharmacodynamics: Mit-lipo dose-dependently inhibited PC-3 tumor growth at a dose ranging from 1 to 4 mg x kg(-1). The antitumor effect studies showed that Mit-lipo significantly improved the therapeutic effect in comparison with free drug. (2) Pharmacokinetics: in comparison with Mit-free, the AUC and t(1/2) values of Mit-lipo at the same dose level were higher than those of Mit-free in Beagle dogs. The results showed that Mit-lipo had long circulation characteristics. (3) Tissue distribution in S-180 bearing mice: compared to Mit-free, Mit-lipo preferentially accumulated into tumor zones instead of normal tissues. Tumor AUC in Mit-lipo treated animals was 8.7 fold higher than that in mice treated with the same dose of Mit-free. The Cmax values of Mit-lipo in heart, kidney, lung, spleen and intestinal tissue in Mit-lipo were 30.2%, 161.6%, 20.2%, 27.9% and 78.3% lower than those of Mit-free, respectively. The pharmacokinetics and tissue distribution of Mit-lipo changed obviously, thus increasing therapeutic effect and improving drug therapeutic index.
