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Abstract
In the present study, we investigated the influence of Cap on digoxin pharmacokinetics in lipopolysaccharide (LPS)-treated rats.
After the oral administration of digoxin (0.1 mg/kg), the area under the plasma concentration-time curve (AUC) of digoxin increased significantly until day 3 after LPS treatment. In the LPS + Cap group, the recovery period of AUC was shortened to 3 days. On days 5 and 7, the maximum plasma concentrations decreased significantly as compared to the control group. The bioavailability of digoxin in LPS group was higher than that in the LPS + Cap group.
The hepatic cytochrome P450 (CYP) 3A2 content decreased significantly until day 5 after LPS administration, but it returned to the control level until 5 days in the LPS + Cap group. Hepatic CYP3A2 mRNA expression of LPS group decreased significantly until day 3, but it returned to the control level on day 3 and increased significantly until day 7 in the LPS + Cap group.
The DNA-binding activity of pregnane X receptor (PXR) was increased on days 3–7 in the Cap and LPS + Cap group.
Cap decreased the absorption of digoxin by inducing CYP3A2 mRNA expression via indirect activation of PXR in LPS-treated rats.
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Acknowledgements
The authors thank Maruishi Pharmaceutical Co., Ltd. for the gift of Cap.
Declaration of interest
The authors report no conflicts of interest.