title: Comparative study of peripheral neurotoxicity after injection of two different paclitaxel formulations in rats.
abstract: Paclitaxel Inj. [NK] (test; paclitaxel, CAS 33069-62-4) is a generic version of the drug from the originator (reference). Both drugs contain the same active ingredient and showed identical pharmacokinetics in patients in the previous study; however, these two drugs may have different safety profiles because they contain different inactive ingredients. Thus, in this study, peripheral neurotoxicity, one of the dose-limiting toxicities of the reference, was compared between the test and the reference in rats electrophysiologically and histopathologically. In a nerve conduction study, the amplitude of the caudal sensory nerve action potential decreased significantly after either the test or the reference administration, compared with the amplitude after saline administration, but no significant differences were observed between the two drugs. Histopathologically, apparent degeneration of the myelinated fibers in the sciatic and the sural nerves was seen after either the test or the reference injection, compared with after saline injection, but no apparent differences were observed between the two formulations. These results suggest that no significant difference in peripheral neurotoxicity exists between the test and the reference in rats.
authors.affiliation: Pharmaceutical Research Laboratories, Research & Development Group, Nippon Kayaku Co., Ltd., Tokyo, Japan. Iwao.Nakamura@nipponkayaku.co.jp
authors.forename: Iwao
authors.initials: I
authors.lastname: Nakamura
authors.forename: Eiji
authors.initials: E
authors.lastname: Ichimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Mashiba
authors.forename: Daichi
authors.initials: D
authors.lastname: Nagai
authors.forename: Keiko
authors.initials: K
authors.lastname: Ebara
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Okamoto
authors.forename: Norio
authors.initials: N
authors.lastname: Wake
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Nishikawa
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D002626:Chemistry, Pharmaceutical; D004594:Electrophysiology; D007267:Injections; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000473:pathology; D011984:Sensory Receptor Cells / Q000187:drug effects; D013497:Sural Nerve / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel