title: Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors.
abstract: OBJECTIVE
  The purpose of this study was to investigate the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of ursolic acid liposomes (UAL), as a new drug, in healthy adult volunteers and patients with advanced solid tumors.
  
  
  METHODS
  All subjects received a single-dose of UAL (11, 22, 37, 56, 74, 98, and 130 mg/m(2)) administered as a 4-h intravenous infusion. Toxicity was assessed and plasma samples were analyzed using validated ultra-performance liquid chromatograph/tandem mass spectroscopy method.
  
  
  RESULTS
  A total of 63 subjects including 4 patients and 35 healthy adult volunteers for toxicity study and 24 healthy adult volunteers for pharmacokinetic study were enrolled in this trial. The DLT was encountered at 74, 98, and 130 mg/m(2), and consisted of hepatotoxicity and diarrhea. Other adverse events included grade 1 nausea, grade 2 abdominal distention, grade 1 microscopic hematuria, grade 2 elevated serum sodium, grade 1 vascular stimulation, and grade 1 skin rash. The MTD was 98 mg/m(2). The single-dose pharmacokinetic parameters revealed a linear relationship between C(max), AUC(0→24 h), or AUC(0→∞) and escalated doses.
  
  
  CONCLUSIONS
  The clinical data reported for the first time that UAL had manageable toxicities with MTD of 98 mg/m(2). The DLT were hepatotoxicity and diarrhea. Meanwhile, UAL had a linear pharmacokinetic profile. The registration number of this trial is ChiCTR-ONC-12002385.
authors.affiliation: Tianjin Medical University, Tianjin Medical University Cancer Hospital and Institute, Sino-US Center for Lymphoma and Leukemia, Department of Lymphoma, Key Laboratory of Cancer Prevention and Therapy, Tiyuanbei, Huanhuxi Road, Hexi District, Tianjin 300060, China.
authors.forename: Xian-Huo
authors.initials: XH
authors.lastname: Wang
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Zhou
authors.forename: Zheng-Zi
authors.initials: ZZ
authors.lastname: Qian
authors.forename: Hui-Lai
authors.initials: HL
authors.lastname: Zhang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Qiu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Song
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Xi-Shan
authors.initials: XS
authors.lastname: Hao
authors.forename: Hua-Qing
authors.initials: HQ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000453:epidemiology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D014315:Triterpenes / Q000008:administration & dosage* / Q000009:adverse effects*; D055815:Young Adult; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D014315:Triterpenes; D000097245:Ursolic Acid