Pharmacokinetics and first-pass effects of liquiritigenin in rats: low bioavailability is primarily due to extensive gastrointestinal first-pass effect.
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.
Kang
H E
HE
College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Cho
Y K
YK
Jung
H Y
HY
Choi
K Y
KY
Sohn
S I
SI
Baek
S R
SR
Lee
M G
MG
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D003956:Dialysis; D044950:Flavanones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008110:Liver Extracts; D008297:Male; D010949:Plasma; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
D044950:Flavanones; D008110:Liver Extracts; C083152:liquiritigenin