Pharmacokinetics and first-pass effects of liquiritigenin in rats: low bioavailability is primarily due to extensive gastrointestinal first-pass effect.
Xenobiotica
; 39(6): 465-75, 2009 Jun.
Article
in En
| MEDLINE
| ID: mdl-19480552
ABSTRACT
Pharmacokinetics of liquiritigenin, a candidate for inflammatory liver disease, and its two glucuronide conjugates, M1 and M2, were evaluated in rats. The hepatic and gastrointestinal first-pass effects of liquiritigenin were also evaluated in rats. After oral administration of liquiritigenin at a dose of 20 mg kg(-1), 1.07% of the dose was not absorbed from the gastrointestinal tract up to 24 h, and the F-value was only 6.68%. In vitro metabolism of liquiritigenin in S9 fractions of rat tissues showed that the liver and intestine were major tissues responsible for glucuronidation of liquiritigenin. The hepatic and gastrointestinal first-pass effects of liquiritigenin were approximately 3.67% and 92.5% of the oral dose, respectively. Although the hepatic first-pass effect of liquiritigenin after absorption into the portal vein was 57.1%, the value was only 3.67% of the oral dose due to extensive gastrointestinal first-pass effect in rats. Therefore, the low F-value of liquiritigenin in rats was primarily attributable to an extensive gastrointestinal first-pass effect although liquiritigenin was well absorbed. Compared with rats, the higher F-value of liquiritigenin could be expected in humans.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gastrointestinal Tract
/
Flavanones
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Xenobiotica
Year:
2009
Type:
Article