Differential effects of chrysin on nitrofurantoin pharmacokinetics mediated by intestinal breast cancer resistance protein in rats and mice.

Abstract

PURPOSE:

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.

• Authors: Atsushi Kawase, Yukako Matsumoto, Motoshi Hadano, Yui Ishii, Masahiro Iwaki
• Journal: Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques (J Pharm Pharm Sci) Vol. 12 Issue 2 Pg. 150-63 ( 2009) ISSN: 1482-1826 [Electronic] Switzerland
• PMID: 19732493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Abcg2 protein, mouse
• Abcg2 protein, rat
• Anti-Infective Agents, Urinary
• Antioxidants
• Flavonoids
• RNA, Messenger
• chrysin
• Nitrofurantoin

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (metabolism)
• Administration, Oral
• Animals
• Anti-Infective Agents, Urinary (administration & dosage, pharmacokinetics)
• Antioxidants (administration & dosage, pharmacology)
• Area Under Curve
• Female
• Flavonoids (administration & dosage, pharmacology)
• Injections, Intraperitoneal
• Injections, Intravenous
• Intestinal Absorption
• Intestine, Small (metabolism)
• Male
• Mice
• Nitrofurantoin (administration & dosage, pharmacokinetics)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Sex Factors
• Species Specificity