| 論文名 |
Quantification of trans-2,6-difluoro-4'-N,N-dimethylaminostilbene in rat plasma: application to a pharmacokinetic study. |
| 著者 |
Hai-Shu Lin
Vitaliy M Sviripa
David S Watt
Chunming Liu
Tian-Xiang Xiang
Bradley D Anderson
Pei Shi Ong
Paul C Ho
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
J Pharm Biomed Anal. 2013 Jan;72:115-20. |
| WEBサイト |
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| 論文概要（和文） |
ラット血漿中のトランス-2,6-ジフルオロ-4'-N、N-ジメチルアミノスチルベンの定量化：薬物動態研究への応用。 |
| 論文概要（英文） |
trans-2,6-Difluoro-4'-N,N-dimethylaminostilbene (DFS), a synthetic stilbene, displayed potent pre-clinical anti-cancer activities exceeding that observed for naturally occurring resveratrol. In this study, a simple and sensitive HPLC method was developed and validated to quantify DFS in rat plasma. The lower limit of quantification (LLOQ) was 5 ng/ml. The intra- and inter-day variation in terms of relative standard deviation (RSD) was all less than 10%. The bias rate ranged from -11.5% to 6.2% while the absolute recovery ranged from 94.1 ± 2.3 to 97.3 ± 4.4%. The pharmacokinetic profiles of DFS were examined in Sprague-Dawley rats after intravenous administration (2 mg/kg). DFS displayed moderate clearance (Cl=61.5 ± 17.7 ml/min/kg) and a relatively prolonged terminal elimination half-life (t(1/2 λz)) of 351 ± 180 min. Aqueous solubility played a crucial role in the oral absorption of DFS. When DFS was given as a suspension (6 mg/kg), the absolute oral bioavailability (F) was almost negligible. However, when DFS was given in a solution prepared with hydroxypropyl-β-cyclodextrin (6 mg/kg), the F was 12.4 ± 10.7%. Dose-escalation to 15 mg/kg resulted in much higher systemic exposure (F=40.2 ± 10.0%). As DFS is orally available after formulation with hydroxypropyl-β-cyclodextrin and pharmacologically active systemic concentrations could be achieved after a single oral dose, the use of DFS as a cancer chemopreventive/chemotherapeutic agent is possible. |
