Pharmacokinetics of selected chiral flavonoids: hesperetin, naringenin and eriodictyol in rats and their content in fruit juices.
The majority of pharmacokinetic studies of individual flavonoids or after ingestion of foodstuffs have overlooked the chirality of some of these xenobiotics. In order to characterize for the first time the stereoselective pharmacokinetics of three flavonoids, hesperetin, naringenin and eriodictyol were intravenously administered (20 mg/kg) to male Sprague-Dawley rats, and their stereospecific content was assessed in various fruit juices. Concentrations in serum, urine and fruit juices were characterized via HPLC and verified by LC/MS. Short half-lives (3-7 h) in serum were observed, while a better estimation of half-life (12-48 h) and the other pharmacokinetic parameters was observed using urinary data. The three flavonoids are predominantly excreted via non-renal routes (fe values of 3-7%), and undergo rapid and extensive phase II metabolism. The (2S)-epimers of the flavonoid glycosides and the S(-)-enantiomers of the aglycones were predominant and in some instances the organic fruit juices had higher concentrations than the conventional fruit juices. This study reports for the first time the stereospecific pharmacokinetics of three chiral flavonoids and their stereospecific content in fruit juices. It also reports for the first time the stereospecific pharmacokinetics of flavonoids employing urine as a more reliable biological matrix.
Department of Pharmaceutical Sciences, and Pharmacology and Toxicology Graduate Program College of Pharmacy, Washington State University Pullman, Washington 99164-6534, USA. jyanez@wsu.edu
Jaime A
JA
Yáñez
Connie M
CM
Remsberg
Nicole D
ND
Miranda
Karina R
KR
Vega-Villa
Preston K
PK
Andrews
Neal M
NM
Davies
D000818:Animals; D019540:Area Under Curve; D001628:Beverages / Q000032:analysis*; D044950:Flavanones / Q000032:analysis / Q000493:pharmacokinetics*; D005638:Fruit / Q000737:chemistry*; D006207:Half-Life; D006569:Hesperidin / Q000032:analysis / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D044950:Flavanones; D006569:Hesperidin; C005273:naringenin; C007619:eriodictyol; C013015:hesperetin