Effect of administration site in the gastrointestinal tract on bioavailability of poorly absorbed drugs taken after a meal.
Food-drug interactions may reduce the bioavailability of drugs taken after meals (negative food effect). In order to develop pharmaceutical technologies that overcome this problem, the effect of administration site within the gastrointestinal tract on the bioavailability of several model drugs was examined in rats. Bioavailability after oral administration to fed animals was one-fifth to one-tenth of that in the fasted animals because of interactions between drugs and large amounts of food components remaining in the stomach. This strong negative food effect was reduced when drugs were administered directly into any site of the small intestine. Bioavailability was maximized when the drug administration site was the middle small intestine. On the other hand, intracolonic administration did not result in the reduction of the negative food effect. Site-specific drug delivery to the middle small intestine could be a useful approach for reducing the negative food effect on drug absorption with maximized bioavailability.
Sakuma
Shinji
S
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan. sakuma@pharm.setsunan.ac.jp
Tanno
Fumié K
FK
Masaoka
Yoshie
Y
Kataoka
Makoto
M
Kozaki
Toshio
T
Kamaguchi
Ryosei
R
Kokubo
Hiroyasu
H
Yamashita
Shinji
S
D000818:Animals; D001682:Biological Availability; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D018565:Food-Drug Interactions; D005772:Gastrointestinal Transit; D007262:Infusions, Intravenous; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009281:Naphthalenes / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011422:Propionates / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D000068296:Risedronic Acid; D014266:Trientine / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D009281:Naphthalenes; D011422:Propionates; D000068296:Risedronic Acid; D012968:Etidronic Acid; D014266:Trientine