التفاصيل البيبلوغرافية
| العنوان: |
Pharmacokinetics and safety of vitamin E δ-tocotrienol after single and multiple doses in healthy subjects with measurement of vitamin E metabolites. |
| المؤلفون: |
Mahipal, Amit, Klapman, Jason, Vignesh, Shivakumar, Yang, Chung, Neuger, Anthony, Chen, Dung-Tsa, Malafa, Mokenge, Yang, Chung S, Malafa, Mokenge P |
| المصدر: |
Cancer Chemotherapy & Pharmacology; Jul2016, Vol. 78 Issue 1, p157-165, 9p |
| مصطلحات موضوعية: |
PANCREATIC cancer treatment, TOCOTRIENOL, DRUG dosage, MEDICATION safety, VITAMIN E, METABOLITES, PHARMACOKINETICS, THERAPEUTICS, ANTINEOPLASTIC agents, CLINICAL trials, COMPARATIVE studies, DRUG administration, DOSE-effect relationship in pharmacology, HIGH performance liquid chromatography, IMMUNITY, RESEARCH methodology, MEDICAL cooperation, RESEARCH, RESEARCH funding, TIME, EVALUATION research |
| مستخلص: |
Purpose: Vitamin E delta-tocotrienol (VEDT) has demonstrated chemopreventive and antineoplastic activity in preclinical models. The aim of our study was to determine the safety and pharmacokinetics of VEDT and its metabolites after single- and multiple-dose administrations in healthy subjects.Methods: Thirty-six subjects received from 100 to 1600 mg of oral VEDT as a single dose or twice daily for 14 consecutive days. A 3 + 3 dose escalation design was utilized. Pharmacokinetic data were derived from high-performance liquid chromatography (HPLC) assays. Serial blood and urine samples were collected before and during VEDT administration, with serum and urine metabolites assessed using HPLC.Results: No drug-related adverse events were observed. Pharmacokinetic parameters for single and multiple doses were, respectively, as follows (shown as range): time to maximum concentration of 4-9.3 and 4.7-7.3 h, maximum concentration of 795.6-3742.6 and 493.3-3746 ng/mL, half-life of 1.7-5.9 and 2.3-6.9 h, and 0-12 h area under the curve of 4518.7-20,781.4 and 1987.7-22,171.2 ng h/mL. Plasma tocotrienols were significantly increased after VEDT administration, indicating oral bioavailability of VEDT in humans. Plasma and urine levels of metabolites, δ-carboxyethyl hydroxychroman, and δ-carboxymethylbutyl hydroxychroman were elevated after VEDT administration in a dose-dependent manner and were 30-60 times significantly higher than δ-tocotrienol levels. VEDT can be safely administered at doses up to 1600 mg twice daily. Plasma VEDT concentrations were comparable to those obtained in VEDT-treated mice in which tumor growth was delayed.Conclusions: Our results suggest that VEDT can be safely consumed by healthy subjects and achieve bioactive levels, supporting the investigation of VEDT for chemoprevention. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
