Introduction of recirculatory analysis into portal and systemic concentration difference method.
Recirculatory analysis was introduced into the portal and systemic concentration difference method with double dosing (PS-DD method), which is an evaluation system for the local intestinal and hepatic first-pass effect. 5-Fluorouracil (5-FU) and cephalexin (CEX) were selected as model drugs. A new recirculatory system was constructed to predict the time courses of a drug concentration in the systemic and portal bloods. Bioavailability (F), local absorption ratio (Fa), hepatic recovery ratio (FH), and local mean absorption time (ta) estimated by recirculatory analysis were close to those calculated by moment analysis with numerical integration. Using recirculatory analysis, the sampling period was considerably shortened and the sampling number was also reduced, which demonstrates that recirculatory analysis is useful in PS-DD method.
Ueda
S
S
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Japan.
Yamaoka
K
K
Sawai
Y
Y
Nakagawa
T
T
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002506:Cephalexin / Q000097:blood* / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005472:Fluorouracil / Q000097:blood* / Q000493:pharmacokinetics; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D008956:Models, Chemical; D011168:Portal System / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002506:Cephalexin; D005472:Fluorouracil