| Title |
Pharmacokinetics and safety of vitamin E δ-tocotrienol after single and multiple doses in healthy subjects with measurement of vitamin E metabolites
|
|---|---|
| Published in |
Cancer Chemotherapy and Pharmacology, June 2016
|
| DOI | 10.1007/s00280-016-3048-0 |
| Pubmed ID | |
| Authors |
Amit Mahipal, Jason Klapman, Shivakumar Vignesh, Chung S. Yang, Anthony Neuger, Dung-Tsa Chen, Mokenge P. Malafa |
| Abstract |
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. 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. 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. Our results suggest that VEDT can be safely consumed by healthy subjects and achieve bioactive levels, supporting the investigation of VEDT for chemoprevention. |
Mendeley readers
The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 54 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 19% |
| Student > Bachelor | 9 | 17% |
| Student > Ph. D. Student | 5 | 9% |
| Student > Master | 4 | 7% |
| Lecturer | 3 | 6% |
| Other | 8 | 15% |
| Unknown | 15 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 13% |
| Agricultural and Biological Sciences | 7 | 13% |
| Biochemistry, Genetics and Molecular Biology | 5 | 9% |
| Medicine and Dentistry | 5 | 9% |
| Psychology | 2 | 4% |
| Other | 8 | 15% |
| Unknown | 20 | 37% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 June 2016.
All research outputs
#21,164,509
of 23,815,455 outputs
Outputs from Cancer Chemotherapy and Pharmacology
#2,211
of 2,501 outputs
Outputs of similar age
#296,716
of 343,460 outputs
Outputs of similar age from Cancer Chemotherapy and Pharmacology
#22
of 33 outputs
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