Influence of capsaicin on fluctuation of digoxin pharmacokinetics in lipopolysaccharide-treated rats

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.

Effects of capsaicin on pharmacokinetics of pitavastatin in rats

“…CAP decreased the bioavailability of digoxin via induction of CYP3A2 mRNA expression by indirectly activating PXR in LPS-treated rats (Kato et al, 2012). The bioavailability of simvastatin, which is mainly metabolized through CYP3A, was reduced after pre-treatment with CAP (Zhai et al, 2013a).…”

Curcumin, Piperine, and Capsaicin: A Comparative Study of Spice-Mediated Inhibition of Human Cytochrome P450 Isozyme Activities

“…CAP, the pungent ingredient of chilli peppers, is another SC shown to modulate P450 isozymes (Takanohashi et al, 2010;Han et al, 2012;Kato et al, 2012). CAP at dietary concentrations may not be a P450 inhibitor, but at concentrations higher than 2.0 mM, it has been shown to inhibit CYP2D6 and CYP1A2 activities sufficiently to impact drug metabolism (Babbar et al, 2010).…”