Enhanced bioavailability of etoposide after oral or intravenous administration of etoposide with kaempferol in rats

Abstract

This study was to investigate the effect of kaempferol on the pharmacokinetics of etoposide after oral or intravenous administration of etoposide in rats. The oral (6 mg/kg) or intravenous (2 mg/kg) etoposide was administered to rats alone or 30 min after the oral kaempferol (1, 4, or 12 mg/kg) administration. Compared to the oral control group, the presence of kaempferol significantly (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) increased the area under the plasma concentrationtime curve (AUC) and the peak concentration (C(max)) of the oral etoposide. Kaempferol decreased significantly (4 or 12 mg/kg, P < 0.05) the total body clearance (CL/F) of oral etoposide, while there was no significant change in the terminal halflife (t(1/2)), the elimination rate constant (K(el)) and the time to reach the peak concentration (T(max)) of etoposide in the presense of kaempferol. Consequently, the absolute bioavailability (AB%) of oral etoposide with kaempferol was significantly higher (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) than those from the control group. Compared to the intravenous control group, the presence of kaempferol enhanced the AUC of intravenously administered etoposide, however, only presence of 12 mg/kg of kaempferol significant (P < 0.05) increased AUC of etoposide. The enhanced bioavailability of oral etoposide by kaempferol could have been due to an inhibition of cytochrom P450 (CYP) 3A and P-glycoprotein (P-gp) in the intestinal or decreased total body clearance in the liver by kaempferol. The dosage regimen of etoposide should be taken into consideration for potential drug interaction when combined with kaempferol or dietary supplements containing kaempferol in patients.

Effects of Kaempferol, an Antioxidant, on the Bioavailability and Pharmacokinetics of Nimodipine in Rats

“…The absolute bioavailability of nimodipine in the presence of kaempferol was significantly enhanced. This result is coincident with the previous study, that the presence of kaempferol significantly increased AUC of tamoxifen (Piao et al, 2008) and that kaempferol significantly increased AUC of etoposide (Li et al, 2009).…”

Astragalin-induced cell death is caspase-dependent and enhances the susceptibility of lung cancer cells to tumor necrosis factor by inhibiting the NF-κB pathway

“…Kaempferol has also been found to exhibit anti-oxidant and cellular membrane protective effects [36]. However, the efflux of kaempferol restricts its potential use as an anticancer agent [37, 38]. Therefore, in the current study, we studied whether the glycoside of kaempferol, AG, has a remarkable bio-activity in lung cancer using a pair of NSCLC cell lines.…”

Simultaneous determination of etoposide and a piperine analogue (PA-1) by UPLC–qTOF-MS: Evidence that PA-1 enhances the oral bioavailability of etoposide in mice

“…The main enzymes involved in the metabolism of etoposide are CYP 3A4 and CYP 1A2. Etoposide is also reported to be a substrate for P-gp [20]. The incomplete and poor oral bioavailability of etoposide has also been attributed to its poor absorption owing to its physicochemical characteristics [21].…”

“…However etoposide has shortcomings of low and variable bioavailability after oral dosing [9,10]. Currently different pharmacological approaches are being explored in order to demonstrate any potentially useful improvement in rate and extent of etoposide absorption into the systemic circulation in the clinical setting of oral therapy [11][12][13][14][15][16][17].…”