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https://doi.org/10.3390/molecules19079577
Title: | Quantification of the resveratrol analogs trans-2,3-dimethoxystilbene and trans-3,4-dimethoxystilbene in rat plasma: Application to pre-clinical pharmacokinetic studies | Authors: | Ng, S.Y Cardullo, N Yeo, S.C.M Spatafora, C Tringali, C Ong, P.-S Lin, H.-S |
Keywords: | 3,4-dimethoxystilbene resveratrol stilbene derivative animal bioavailability chemistry drug screening drug stability high performance liquid chromatography liver microsome male metabolism rat reproducibility Animals Biological Availability Chromatography, High Pressure Liquid Drug Evaluation, Preclinical Drug Stability Male Microsomes, Liver Rats Reproducibility of Results Stilbenes |
Issue Date: | 2014 | Publisher: | MDPI AG | Citation: | Ng, S.Y, Cardullo, N, Yeo, S.C.M, Spatafora, C, Tringali, C, Ong, P.-S, Lin, H.-S (2014). Quantification of the resveratrol analogs trans-2,3-dimethoxystilbene and trans-3,4-dimethoxystilbene in rat plasma: Application to pre-clinical pharmacokinetic studies. Molecules 19 (7) : 9577-9590. ScholarBank@NUS Repository. https://doi.org/10.3390/molecules19079577 | Abstract: | trans-2,3-Dimethoxystilbene (2,3-DMS) and trans-3,4-dimethoxystilbene (3,4-DMS) are two synthetic resveratrol (trans-3,5,4'- Trihydroxystilbene) analogs. In this study, a simple HPLC method was developed and validated to determine 2,3-DMS and 3,4-DMS in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC column through a 12.5-min gradient delivery of a mixture of acetonitrile and water at the flow rate of 1.5 mL/min at 50 °C. The lower limit of quantification was 10 ng/mL. After successful validation, the pharmacokinetic profiles of 2,3-DMS and 3,4-DMS were subsequently studied in Sprague-Dawley rats. Upon single intravenous administration (4 mg/kg), 2,3-DMS had a medium volume of distribution of the central compartment (Vc = 2.71 ± 0.51 L/kg), quite rapid clearance (Cl = 52.0 ± 7.0 mL/min/kg), moderate mean transit time (MTT0?last= 131.0 ± 4.5 min) but a fairly long terminal elimination half-life (t1/2 ?Z= 288.9 ± 92.9 min). Interestingly, 3,4-DMS displayed a pharmacokinetic profile apparently distinct from 2,3-DMS and it had more extensive distribution (Vc = 5.58 ± 1.73 L/kg), faster clearance (Cl = 143.4 ± 40.5 mL/min/kg) and shorter residence (MTT0?last = 61.4 ± 27.1 min). Following single oral administration (10 mg/kg), 2,3-DMS had low and erratic plasma exposure (Cmax = 37.5 ± 23.7 ng/mL) and poor oral bioavailability (2.22% ± 2.13%) while the oral bioavailability of 3,4-DMS was even poorer than 2,3-DMS. Clearly, the location of the methoxy groups had a significant impact on the pharmacokinetics of resveratrol analogs. This study provided useful information for the design of resveratrol derivatives in future study. | Source Title: | Molecules | URI: | https://scholarbank.nus.edu.sg/handle/10635/175319 | ISSN: | 1420-3049 | DOI: | 10.3390/molecules19079577 |
Appears in Collections: | Staff Publications Elements |
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