TY - JOUR T1 - Effect of probiotics on pharmacokinetics of orally administered acetaminophen in mice JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.117.077222 SP - dmd.117.077222 AU - Jeon-Kyung Kim AU - Min Sun Choi AU - Jin-Ju Jeong AU - Su-Min Lim AU - In Sook Kim AU - Hye Hyun Yoo AU - Dong-Hyun Kim Y1 - 2017/01/01 UR - http://dmd.aspetjournals.org/content/early/2017/12/05/dmd.117.077222.abstract N2 - Orally administered probiotics change gut microbiota composition and enzyme activities. Thus, coadministration of probiotics with drugs may lead to changes in the pharmacokinetic parameters of the drugs. In this study, we investigated the pharmacokinetics of acetaminophen in rats treated with probiotics. Oral administration of probiotics changed the gut microbiota composition in the mice. Of these probiotics, Lactobacillus reuteri K8 increased the numbers of clostridia, bifidobacteria, and enterococci, and Lactobacillus rhamnosus K9 decreased the number of bifidobacteria, determined by culturing in selective media. Next, we performed a pharmacokinetic study of acetaminophen in mice orally treated with K8 and K9 for three days. Treatment with K8 reduced the area under the curve (AUC) of orally administered acetaminophen to 68.4% compared to normal control mice, whereas K9 did not affect the AUC of acetaminophen. Oral administration to mice of K8, which degraded acetaminophen, increased the degradation of acetaminophen by gut microbiota, whereas K9 treatment did not affect it. Treatment with K8 increased the number of Lactoacillus reuteri adhered in the upper small intestine, whereas the number of Lactobacillus rhamnosus was not affected by treatment with K8 or K9. K8 increased the number of cyanobacteria, whereas K9 increased the number of deferribacteres. These results suggest that the intake of probiotics may make the absorption of orally administered drugs fluctuate through the disturbance of gut microbiota-mediated drug metabolism and that the subsequent impact on microbiota metabolism could result in altered systemic concentrations of the intact drug. ER -