Influence of long-term enteral nutrition on pharmacokinetics of digoxin in rats.
This study was designed to clarify the influence of long-term enteral nutrition (EN) on the pharmacokinetics of digoxin. Rats were fed EN diets (semi-digested, digested, and elemental) for 4 weeks, then digoxin (0.05 mg/kg) was administered orally. The AUC(0-∞) and k(a) of digoxin were significantly reduced in the semi-digested diet group versus the control, while the AUC(0-∞) was significantly increased in the digested and elemental diet groups. The mRNA level of Slco1a4 was significantly reduced at the upper small intestine in all EN groups. Further, the expression levels of P-glycoprotein (P-gp) protein and Abcb1a mRNA were increased at the same site in all EN groups, and the increases were significant in the elemental diet group. Cyp3a2 protein and mRNA expressions were significantly reduced in the liver in the digested and elemental diet groups. Abcb1a mRNA was also significantly reduced in the kidney in these groups. These results indicate that the absorption kinetics at the small intestine is influenced by semi-digested diet, and the elimination kinetics in the liver and kidney are influenced by digested and elemental diet. Semi-digested diet also altered digoxin pharmacokinetics in humans. Thus, the effect of long-term EN on digoxin pharmacokinetics depended on the dietary components.
Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan. .
Keiichiro
K
Higashi
Chihiro
C
Tanaka
Kaori
K
Imanishi
Kazuki
K
Sawamoto
Takumi
T
Horikawa
Hiroko
H
Ohkawa
Ryo
R
Matsushita
Yoshimichi
Y
Sai
Ken-ichi
K
Miyamoto
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D001835:Body Weight; D002316:Cardiotonic Agents / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004077:Digoxin / Q000493:pharmacokinetics*; D004750:Enteral Nutrition; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002316:Cardiotonic Agents; D008565:Membrane Proteins; D004077:Digoxin; C095122:multidrug resistance protein 3; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A