Pharmacokinetics of selected stilbenes: rhapontigenin, piceatannol and pinosylvin in rats.
The pharmacokinetics of piceatannol, pinosylvin and rhapontigenin were characterized in male Sprague-Dawley rats after single intravenous doses of 10 mg kg(-1) of each stilbene. Serial blood samples were collected via a catheter inserted into the right jugular vein and plasma samples were analysed for the selected stilbenes concentrations using reverse phase HPLC methods. After an acute intravenous dose of piceatannol, plasma AUC, urine t(1/2), CL and V(d) were 8.48+/-2.48 micro g h mL(-1), 19.88+/-5.66 h, 2.13+/-0.92 Lh(-1) kg(-1) and 10.76+/-2.88 L kg(-1)(mean+/-s.e.m.), respectively. The acute intravenous dose of pinosylvin yielded the plasma AUC, urine t(1/2), CL and V(d) values of 5.23+/-1.20 micro g h mL(-1), 13.13+/-2.05 h, 1.84+/-0.44 Lh(-1) kg(-1) and 2.29+/-0.56 L kg(-1)(mean+/-s.e.m.), respectively. Rhapontigenin intravenous dosing yielded the plasma AUC, urine t(1/2), CL and V(d) values of 8.39+/-0.10 micro g h mL(-1), 25.31+/-1.46 h, 1.18+/-0.035 Lh(-1) kg(-1) and 11.05+/-0.17 L kg(-1)(mean+/-s.e.m.), respectively. Each stilbene was extensively glucuronidated. These stilbenes were predominantly eliminated via non-urinary routes. All three stilbenes were highly distributed into tissues and were highly extracted by the liver. The detectable plasma half-lives of these xenobiotics appear to be relatively short. However, utilizing urinary concentration-time data, much longer elimination half-lives were evident. The estimates of oral bioavailability characterize these stilbenes as poorly bioavailable compounds.
Roupe
Kathryn A
KA
Department of Pharmaceutical Sciences, and Pharmacology and Toxicology Graduate Program, College of Pharmacy, Washington State University Pullman, WA 99164-6534, USA.
Yáñez
Jaime A
JA
Teng
Xiao Wei
XW
Davies
Neal M
NM
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013267:Stilbenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D000094162:Phytoalexins
D013267:Stilbenes; C431126:rhapontigenin; C041525:3,3',4,5'-tetrahydroxystilbene; C049032:pinosylvin; D000094162:Phytoalexins