title: A novel paclitaxel microemulsion containing a reduced amount of Cremophor EL: pharmacokinetics, biodistribution, and in vivo antitumor efficacy and safety.
abstract: The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had similar pharmacokinetics and antitumor efficacy as the commercially available PTX injection, but a significantly reduced allergic effect due to the CrEL. The pharmacokinetics, biodistribution, in vivo antitumor activity and safety of PTX microemulsion was evaluated. The results of pharmacokinetic and distribution properties of PTX in the microemulsion were similar to those of the PTX injection. The antitumor efficacy of the PTX microemulsion in OVCRA-3 and A 549 tumor-bearing animals was similar to that of PTX injection. The PTX microemulsion did not cause haemolysis, erythrocyte agglutination or simulative reaction. The incidence and degree of allergic reactions exhibited by the PTX microemulsion group, with or without premedication, were significantly lower than those in the PTX injection group (P < .01). In conclusion, the PTX microemulsion had similar pharmacokinetics and anti-tumor efficacy to the PTX injection, but a significantly reduced allergic effect due to CrEL, indicating that the PTX microemulsion overcomes the disadvantages of the conventional PTX injection and is one way of avoiding the limitations of current injection product while providing suitable therapeutic efficacy.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ke-Chun
authors.initials: KC
authors.lastname: Wu
authors.forename: Bing-Xiang
authors.initials: BX
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Nie
authors.forename: Wei-San
authors.initials: WS
authors.lastname: Pan
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004285:Dogs; D004655:Emulsions / Q000009:adverse effects / Q000737:chemistry; D005260:Female; D005990:Glycerol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000009:adverse effects / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D014677:Pharmaceutical Vehicles; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol