title: A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors.
abstract: BACKGROUND
  Ursolic acid is a promising anticancer agent. The current study aims to evaluate the single- and multiple-dose pharmacokinetics (PK) as well as the safety of ursolic acid nanoliposomes (UANL) in healthy volunteers and in patients with advanced solid tumors.
  
  
  METHODS
  Twenty-four healthy volunteers in the single-dose PK study were divided into three different groups, which received 37, 74, and 98 mg/m(2) of UANL. Eight patients in the multiple-dose PK study were administered with 74 mg/m(2) of UANL daily for 14 days. The UA plasma concentrations were determined using ultra-performance liquid chromatograph-tandem mass spectrometry.
  
  
  RESULTS
  The plasma concentration profiles of all subjects were characterized by a biexponential decline after infusion. The mean peak plasma concentration (C(max)) increased linearly as a function of the dose (r = 0.999). The mean area under the plasma concentration-time curve (AUC) from 0 to 16 hours also increased proportionally with dose escalation (r = 0.998). However, the clearance was constant over the specific dose interval. In the multiple-dose PK study, the trough and average concentrations remained low. The mean AUC, half-life, C(max), time to C(max), and the volume of distribution on the first day were similar to those on the last day. All subjects tolerated the treatments well. Most UANL-associated adverse events varied from mild to moderate.
  
  
  CONCLUSIONS
  UANL exhibits relatively linear PK behavior with dose levels from 37 mg/m(2) to 98 mg/m(2). No drug accumulation was observed with repeated doses of UANL. The intravenous infusion of UANL was well tolerated by healthy volunteers and patients with advanced tumors.
authors: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
authors: Zhongling
authors: Z
authors: Zhu
authors: Zhengzi
authors: Z
authors: Qian
authors: Zhao
authors: Z
authors: Yan
authors: Cuicui
authors: C
authors: Zhao
authors: Huaqing
authors: H
authors: Wang
authors: Guoguang
authors: G
authors: Ying
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D050997:Nanomedicine; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry; D014315:Triterpenes / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000097245:Ursolic Acid
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: nanoliposomes; pharmacokinetics; solid tumor; tandem mass spectrometry; ultra-performance liquid chromatography; ursolic acid