Pharmacokinetics, tissue distribution and excretion study of resveratrol and its prodrug 3,5,4'-tri-O-acetylresveratrol in rats.
3,5,4'-Tri-O-acetylresveratrol (TARES) synthesized by acetylating three hydroxyl groups of resveratrol (RES) is a prodrug of RES. The aim of this study was to investigate and compare the pharmacokinetics, tissue distribution and excretion of TARES and RES in rats following a single intragastric gavage (i.g.) administration. After RES is transformed into TARES, its pharmacokinetic properties are improved, such as the t1/2 has been prolonged and the AUC has been enhanced. And TARES follows linear plasma pharmacokinetics across the investigated dosage range in rats (77.5-310 mg/kg). The major distribution tissues of TARES or RES in rats were liver, spleen, heart and lung. TARES can increase the content of RES in lung significantly. There was no long-term accumulation of RES in rat tissues. Whether we administrated to rats of equimolar TARES or RES, total recoveries of RES in urine and feces within 36 h were low (0.99% or 0.07% in urine and 1.69% or 0.15% in feces).
Department of Medicinal Chemistry and Pharmaceutical Analysis, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, China.
Li
L
Liang
Xueying
X
Liu
Qingwei
Q
Wang
Sikun
S
Cheng
Shengyong
S
Zhang
Meng
M
Zhang
D000818:Animals; D019540:Area Under Curve; D005243:Feces; D006207:Half-Life; D006321:Heart; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011355:Prodrugs / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013154:Spleen / Q000378:metabolism*; D013267:Stilbenes / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D011355:Prodrugs; D013267:Stilbenes; D000077185:Resveratrol