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.
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Authors | Zhongling Zhu, Zhengzi Qian, Zhao Yan, Cuicui Zhao, Huaqing Wang, Guoguang Ying |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 8
Pg. 129-36
( 2013)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 23319864
(Publication Type: Clinical Trial, Phase I, Journal Article)
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Chemical References |
- Antineoplastic Agents
- Liposomes
- Triterpenes
- ursolic acid
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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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