Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors
| Autor: | Shi Yong Zhou, Xianhuo Wang, Zheng Zi Qian, Huaqing Wang, Zheng Song, Ping Wang, Xi Shan Hao, Li Hua Qiu, Hui Lai Zhang, Jing Zhao |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Drug medicine.medical_specialty Gastrointestinal Diseases Nausea media_common.quotation_subject Toxicology Gastroenterology Cohort Studies Young Adult chemistry.chemical_compound Pharmacokinetics Ursolic acid Neoplasms Internal medicine medicine Humans Infusions Intravenous Adverse effect media_common Pharmacology Dose-Response Relationship Drug business.industry General Medicine Middle Aged Antineoplastic Agents Phytogenic Rash Triterpenes Diarrhea chemistry Anesthesia Liposomes Toxicity Female Chemical and Drug Induced Liver Injury medicine.symptom business Follow-Up Studies |
| Zdroj: | Expert Opinion on Drug Metabolism & Toxicology. 9:117-125 |
| ISSN: | 1744-7607 1742-5255 |
| DOI: | 10.1517/17425255.2013.738667 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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