Differential effects of chrysin on nitrofurantoin pharmacokinetics mediated by intestinal breast cancer resistance protein in rats and mice.
OBJECTIVE
The activities of breast cancer resistance protein (Bcrp/ABCG2) as well as P-glycoprotein (P-gp) and drug-metabolizing enzymes can be inhibited by several flavonoids or drugs in rats. However, the species, gender and regional differences of effects of flavonoids on Bcrp/ABCG2 in rats and mice remain unclear, although Bcrp, like P-gp, is also important in controlling drug absorption and disposition.


METHODS
We used chrysin as a model flavonoid because it possesses anti-inflammatory and antioxidative properties and is used as a dietary supplement. We examined the pharmacokinetics of nitrofurantoin, a specific Bcrp substrate, in rats and mice treated with chrysin. Bcrp mRNA levels were measured in liver, kidney, duodenum, jejunum and ileum in rats and mice.


RESULTS
Plasma concentrations of nitrofurantoin were increased in rats, but not mice, treated with oral chrysin, compared with untreated controls. Intraperitoneal injection of chrysin into rats or mice had little effect on the elimination of nitrofurantoin, compared with untreated animals.


CONCLUSIONS
These results suggest that chrysin-nitrofurantoin interactions occur in the small intestine in rats, but not in mice, possibly due to the higher levels of Bcrp expression in the small intestine in rats, compared with those in mice.
Kawase
Atsushi
A
School of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Matsumoto
Yukako
Y
Hadano
Motoshi
M
Ishii
Yui
Y
Iwaki
Masahiro
M
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000008:administration & dosage / Q000493:pharmacokinetics; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D019540:Area Under Curve; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D051379:Mice; D009582:Nitrofurantoin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013045:Species Specificity
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; C489249:Abcg2 protein, rat; D000892:Anti-Infective Agents, Urinary; D000975:Antioxidants; D005419:Flavonoids; D012333:RNA, Messenger; C043561:chrysin; D009582:Nitrofurantoin