Effects of CpG-DNA from Escherichia coli on digoxin pharmacokinetics
Ryuji Kato1, Yuka Tokunaga, Takako Kawai
1Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Japan.
Abstract:
Deoxyribonucleic acid (DNA) from bacteria or viruses has been reported as one of the pathogen-associated molecular patterns (PAMPs) and a substance that can induce endotoxemia-like inflammation in animals. However, there has been no report on digoxin pharmacokinetics in the inflammation induced by bacterial DNA containing unmethylated CpG motifs (CpG-DNA). In this study, we investigated the effects of CpG-DNA on digoxin pharmacokinetics. We determined the degree of lipopolysaccharide contamination in CpG-DNA solution and examined the changes in digoxin pharmacokinetics in rats after CpG-DNA administration. In addition, plasma concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and nitrite/nitrate (NOx) were determined after CpG-DNA administration (5 mg/kg, i.p.). The AUC0-24 of digoxin increased significantly on Day 1-3 and CL/F decreased on Day 1 and Day 2 after CpG-DNA administration. On Day 7 after CpG-DNA administration, there were no significant differences in AUC0-24 and CL/F compared with the control group (without CpG-DNA administration). However, Kel remained relatively unchanged throughout the experiment. Plasma TNF-alpha concentrations were significantly increased at 1 h and plasma IL-1beta concentrations were significantly decreased at 6 h after administration of CpG-DNA, while plasma NOx concentrations were significantly increased at 12 h after CpG-DNA administration, compared with the control group. These findings suggest that CpG-DNA (5 mg/kg) induces a transient inflammatory condition, and that AUC0-24 and CL/F of digoxin were altered after CpG-DNA administration. Digoxin pharmacokinetics recovered within 7 d after CpG-DNA exposure.
More Related Videos
06:30Using Microtiter Dish Radiolabeling for Multiple In Vivo Measurements Of Escherichia coli (p)ppGpp Followed by Thin Layer Chromatography
Published on: June 4, 2019
07:04Site-Directed Mutagenesis for In Vitro and In Vivo Experiments Exemplified with RNA Interactions in Escherichia Coli
Published on: February 5, 2019
Related Concept Videos
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Pharmacodynamic Models: Linear Concentration–Effect Model
Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Excretion
Pharmacokinetics: Drug–Drug Interactions
