Effects of morin on the pharmacokinetics of etoposide in rats

Abstract

This study investigated the effects of orally administered morin, an inhibitor of CYP isozyme and P-glycoprotein (P-gp), on the pharmacokinetics of intravenous and orally administered etoposide in rats. It was reported that etoposide is a substrate for P-gp and metabolized mainly via CYP3A4 and to a lesser degree via CYP1A2 and 2E1. Etoposide was administered through intravenous (2 mg/kg) or oral (6 mg/kg) routes to rats with or without orally administered morin (5 or 15 mg/kg), which was administered 30 min before etoposide. The pharmacokinetic parameters of etoposide intravenously administered were not significantly different from other groups, suggesting that CYP 3A-mediated metabolism and the P-gp mediated efflux of etoposide in the liver and kidney seemed not to be markedly inhibited by orally administered morin. However, orally administered morin (15 mg/kg) significantly increased the AUC (45.8%), C(max) (32.0%) and the absolute bioavailability (35.9%) of orally administered etoposide compared with the control, which could be mainly due to inhibition of CYP isoenzyme and P-gp in the intestine by morin. The dosage regimen of etoposide should be taken into consideration for toxic reactions when combined with morin or dietary supplements containing morin in patients.

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

“…This result is coincident with the previous study, that the presence of kaempferol significantly increased AUC and C max of tamoxifen, a P-gp and CYP3A4 substrate (Piao et al, 2008), and the presence of morin, a flavonoid, significantly increased AUC and C max of etoposide, by inhibited the P-gp and CYP3A4 in rats intestine and/or liver (Li et al, 2007). Ofer et al 2005, reported efflux of talinolol across Caco-2 cells was reduced by kaempferol without replacement of talinolol from its binding to P-gp.…”

“…The plasma concentrations of etoposide were determined by a HPLC assay and a modification of the method reported by previous study (Li et al, 2007). Briefly, 0.5 µL of 50 ng/mL podophyllotoxin and 1.2 mL of tertbutylmethylether were mixed with 0.2 mL of the plasma sample in a 2.0 mL polypropylene microtube.…”

Effects of verapamil on etoposide pharmacokinetics after intravenous and oral administration in rats

“…The plasma concentrations of etoposide were determined by HPLC assay, as reported by Li et al (15). Briefly, a 50-!.d aliquot of podophyllotoxin (50 ng/ml dissolved in methanol; internal standard) and a 1.2 ml aliquot of tert-butylmethylether were mixed with a 0.2 ml aliquot of plasma sample in a 2.0 rnl polypropylene microtube (Axygen Scientific Co., CA., USA).…”

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

“…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].…”