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A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors.

AbstractBACKGROUND:
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.
AuthorsZhongling Zhu, Zhengzi Qian, Zhao Yan, Cuicui Zhao, Huaqing Wang, Guoguang Ying
JournalInternational journal of nanomedicine (Int J Nanomedicine) Vol. 8 Pg. 129-36 ( 2013) ISSN: 1178-2013 [Electronic] New Zealand
PMID23319864 (Publication Type: Clinical Trial, Phase I, Journal Article)
Chemical References
  • Antineoplastic Agents
  • Liposomes
  • Triterpenes
  • ursolic acid
Topics
  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents (adverse effects, blood, pharmacokinetics, therapeutic use)
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Liposomes (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
  • Male
  • Middle Aged
  • Nanomedicine
  • Neoplasms (blood, drug therapy, metabolism)
  • Statistics, Nonparametric
  • Tandem Mass Spectrometry
  • Triterpenes (adverse effects, blood, pharmacokinetics, therapeutic use)

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