title: Safety and pharmacokinetic evaluation of repeated intravenous administration of palonosetron 0.75 mg in patients receiving highly or moderately emetogenic chemotherapy.
abstract: OBJECTIVE
  The aims of this study were to evaluate the safety, efficacy, and pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in Japanese patients who received highly or moderately emetogenic chemotherapy.
  
  
  METHODS
  Twenty- six patients received palonosetron 0.75 mg intravenously before chemotherapy on days 1 and 3 plus dexamethasone (12-16 mg before chemotherapy on day 1 and 4-8 mg on days 2 and 3). The primary endpoints were safety and pharmacokinetics. Pharmacokinetics were evaluated in a subset of patients (n=6). Complete response and complete protection were evaluated as secondary endpoints.
  
  
  RESULTS
  The accumulation ratios for C max and AUClast after the second dose on day 3 were 1.42 and 1.37, respectively. These values were consistent with the theoretical values expected from the half-life of palonosetron on day 1. Almost all of the patients had no nausea or vomiting in the acute phase (complete response (CR) rate, 96.2% [25/26]; CP rate, 92.3% [24/26]). In the delayed phase (24-192 h post-chemotherapy), the complete response and complete protection rates were 76.9% (20/26) and 61.5% (16/26), respectively. Treatment was well tolerated.
  
  
  CONCLUSIONS
  This is the first study to report the pharmacokinetics of multiple doses of palonosetron 0.75 mg, given on days 1 and 3, in Japanese patients. Repeated treatment with palonosetron was safe and well tolerated by patients who received highly or moderately emetogenic anticancer chemotherapy.
authors.affiliation: Division of Medical Oncology, Hematology and Infectious Diseases, Department of Internal Medicine, School of Medicine, Fukuoka University, Nanakuma, Jyonan-ku, Fukuoka, Japan, yoikari@fukuoka-u.ac.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ikari
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ogata
authors.forename: Yuta
authors.initials: Y
authors.lastname: Nakashima
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sato
authors.forename: Michio
authors.initials: M
authors.lastname: Masaki
authors.forename: Hiroo
authors.initials: H
authors.lastname: Katsuya
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Goto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishitsuka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takamatsu
authors.forename: Shuuji
authors.initials: S
authors.lastname: Hara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D014839:Vomiting / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D007546:Isoquinolines; D011812:Quinuclidines; D012702:Serotonin Antagonists; D000077924:Palonosetron; D003907:Dexamethasone