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

• Published in: International journal of nanomedicine Vol. 8; no. 1; pp. 129 - 136
• Main Authors: Yan, Zhao, Zhu, Qian, Zhao, Cuicui, Wang, Ying
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2013; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - blood; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Area Under Curve; Cancer; Care and treatment; Chromatography, High Pressure Liquid; Female; Humans; Liposomes - administration & dosage; Liposomes - adverse effects; Liposomes - pharmacokinetics; Liposomes - therapeutic use; Male; Middle Aged; nanoliposomes; Nanomedicine; Nanoparticles; Neoplasms - blood; Neoplasms - drug therapy; Neoplasms - metabolism; Pharmacokinetics; Pharmacology, Experimental; Plasma; Properties; Rapid Communication; solid tumor; Statistics, Nonparametric; Tandem Mass Spectrometry; Terpenes; Triterpenes - adverse effects; Triterpenes - blood; Triterpenes - pharmacokinetics; Triterpenes - therapeutic use; ultra-performance liquid chromatography; Ursolic Acid; pharmacokinetics; solid tumor; tandem mass spectrometry; ultra-performance liquid chromatography; nanoliposomes; ursolic acid
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S38271

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. 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. 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. 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.