title: [Pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone hydrochloride].
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.
authors.affiliation: Hebei Pharmaceutical Technology and Engineering Research Center, Shijiazhuang 050051, China.
authors.forename: Cai-xia
authors.initials: CX
authors.lastname: Wang
authors.forename: Chun-lei
authors.initials: CL
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.forename: Han-yu
authors.initials: HY
authors.lastname: Yang
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.forename: Yan-hui
authors.initials: YH
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008942:Mitoxantrone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000473:pathology; D012510:Sarcoma 180 / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D008942:Mitoxantrone