Pharmacokinetics of magnolin in rats

Abstract

This study was first conducted to characterize the intravenous and oral pharmacokinetics of magnolin, a major pharmacologically active ingredient of Magnolia fargesii, at various doses in rats. Magnolin was administered to rats by intravenous injection (0.5, 1 and 2 mg/kg doses) and oral administration (1, 2 and 4 mg/kg doses), and serial plasma and urine samples were harvested. Magnolin concentrations were determined by a validated LC/MS/MS assay. After both intravenous and oral administration, the AUCs were linearly increased as the dose increased. Other pharmacokinetic parameters of magnolin (except the V ( ss ) after the intravenous administration) were also independent of the doses. The extent of absolute oral bioavailability ranged from 54.3-76.4% for the oral doses examined. Magnolin was considerably bound to rat plasma proteins and the binding value was constant (71.3-80.5%) over a concentration ranging from 500 to 10000 ng/mL. The pharmacokinetic parameters of magnolin were dose-independent after both intravenous and oral administration. When given orally, magnolin was rapidly absorbed.

Tetrahydrofurofuranoid Lignans, Eudesmin, Fargesin, Epimagnolin A, Magnolin, and Yangambin Inhibit UDP-Glucuronosyltransferase 1A1 and 1A3 Activities in Human Liver Microsomes

“…Additionally, the AUC and C max values of magnolin in rats were 7568 ± 1085 ng•h/mL and 2493 ± 513 ng/mL, respectively, when administered NDC-052 (22.2 mg/kg containing 4 mg/kg of magnolin) [20] and had similar results with the previous report [18]. However, the AUC and C max values of magnolin in rats were 3630 ± 581 ng•h/mL and 1340 ± 113 ng/mL, respectively, when administered magnolin alone (4 mg/kg) [21]. These results suggested the possibility of drug interactions among the constituents of herbal drugs.…”

“…In a previous study, the AUC of magnolin was linearly increased with an increase in the intravenous dose (0.5-2 mg/kg) and in the oral dose (1-4 mg/kg) [21]. In addition, magnolin was mainly eliminated by metabolism [21]. Three major metabolites (i.e., Odesmethylmagnolin, i.e., M1 and M2, and hydroxymagnolin, M4) were formed by CYP2C8, CYP2C9, CYP2C19, and CYP3A4 in the in vitro studies of magnolin metabolism [43].…”

“…In a previous study, the AUC of magnolin was linearly increased with an increase in the intravenous dose (0.5-2 mg/kg) and in the oral dose (1-4 mg/kg) [21]. In addition, magnolin was mainly eliminated by metabolism [21].…”

Antiproliferative potential of Physalis peruviana-derived magnolin against pancreatic cancer: a comprehensive in vitro and in silico study

“…It is worth noting that magnolin was found to be rapidly absorbed when it was administered orally, and generally, it has achieved good bioavailability in experimental rats. 65 Accordingly, future in vivo evaluations will be of utmost importance to further develop this natural product into a new antiproliferative therapeutic agent.…”

Liquid chromatography–atmospheric pressure chemical ionization tandem mass spectrometry for the simultaneous determination of dimethoxyaschantin, dimethylliroresinol, dimethylpinoresinol, epimagnolin A, fargesin and magnolin in rat plasma

“…Magnolin has been reported to be metabolized to 4′‐ O ‐demethylmagnolin, 4′′‐ O ‐demethylmagnolin, and their glucuronides in rats (Miyazawa, kasahara, kameoka, 1993) We previously reported a high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS) method for the simultaneous determination of magnolin and epimagnolin A in rat plasma, and the pharmacokinetics of magnolin and epimagnolin A were determined after the oral administration of a purified extract of dried flower buds of Magnolia fargesii at a dose of 22.22 mg/kg in rats (Kim et al ., 2009b). The intravenous and oral pharmacokinetics of magnolin were characterized at various doses in rats (Kim et al ., 2010b).…”