Influence of Long-term Enteral Nutrition on Pharmacokinetics of Digoxin in Rats

• Published in: DRUG METABOLISM AND PHARMACOKINETICS Vol. 28; no. 1; pp. 44 - 52
• Main Authors: Higashi, Keiichiro, Tanaka, Chihiro, Imanishi, Kaori, Sawamoto, Kazuki, Horikawa, Takumi, Ohkawa, Hiroko, Matsushita, Ryo, Sai, Yoshimichi, Miyamoto, Ken-ichi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2013; Japanese Society for the Study of Xenobiotics
• Subjects: absorption; Animals; ATP Binding Cassette Transporter, Sub-Family B - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Body Weight; Cardiotonic Agents - pharmacokinetics; Cyp3a2; Cytochrome P-450 CYP3A - genetics; digoxin; Digoxin - pharmacokinetics; Enteral Nutrition; Male; Membrane Proteins - genetics; metabolism; Oatp; Organ Size; P-gp; pharmacokinetics; Rats; Rats, Sprague-Dawley; enteral nutrition; P-gp; absorption; pharmacokinetics; metabolism; Cyp3a2; digoxin; Oatp
• ISSN: 1347-4367; 1880-0920
• DOI: 10.2133/dmpk.DMPK-11-RG-153

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 (0.05mg/kg) was administered orally. The AUC0-∞and ka of digoxin were significantly reduced in the semi-digested diet group versus the control, while the AUC0-∞ 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.