Inhibition of ABCG2/BCRP transporter by soy isoflavones genistein and daidzein: Effect on plasma and milk levels of danofloxacin in sheep

Effects of triclabendazole on secretion of danofloxacin and moxidectin into the milk of sheep: Role of triclabendazole metabolites as inhibitors of the ruminant ABCG2 transporter

“…Conditions for HPLC analysis of danofloxacin were modified in accordance with Perez et al (2013). Marbofloxacin (Sigma-Aldrich) was used as an internal standard and samples were extracted with chloroform.…”

“…Drug-drug interactions mediated by ABC transporters include increased plasma availability and potentiation of the macrocyclic lactones ivermectin and moxidectin after coadministration of the anthelmintic triclabendazole (TCBZ) or inhibitors of the ABC transporter P-glycoprotein (Lifschitz et al, 2009;McKellar and Gokbulut, 2012). In Assaf sheep, secretion of danofloxacin into milk is reduced on coadministration with the macrocyclic lactone ivermectin (Real et al, 2011a) or by supplementation with a soyenriched diet (Perez et al, 2013).…”

Interaction of Isoflavones with the BCRP/ABCG2 Drug Transporter

“…In addition, the BL-to-AP transport of mitoxantrone was attenuated by biochanin A (5 μM) in MDCK/Bcrp cells [88]. Together, genistein and daidzein (100 μM each) reduced the BL-to-AP transport of BCRP substrates, nitrofurantoin and danofloxacin, in MDCK/BCRP and MDCK/Bcrp cells [89, 127], respectively. Even further, a combination of multiple flavonoids including biochanin A and genistein (apigenin, biochanin A, chrysin, genistein kaempferol, 1 μM total flavonoid) increased the accumulation of mitoxantrone in MCF-7/MX100 cells to a greater extent (EC 50 : 0.23 ± 0.08 μM) than each individual flavonoid (i.e., genistein EC 50 : 14.9 ± 2.69 μM).…”

“…Because genistein and daidzein are often found together in nature, Perez et al [127, 132] examined the effect of a combined isoflavone exposure on the distribution of BCRP substrates danofloxacin and nitrofurantoin into the milk of lactating sheep. Danofloxacin is an antibiotic used in veterinary medicine to treat a broad range of bacterial infections.…”

“…In the danofloxacin experiment, lactating sheep received a 15-day soy supplemented diet that significantly reduced the milk AUC and C max of danofloxacin compared to the sheep that received regular forage without isoflavones [127]. Interestingly, the sheep that received an oral dose of genistein and daidzein (10 mg/kg genistein + 10 mg/kg daidzein) did not demonstrate a similar decrease in milk concentrations of danofloxacin suggesting that the form in which the compounds are administered (i.e., liquid vs. solid, aglycone vs. glycone) or presence of other compounds in the diet may determine its effect on the pharmacokinetics of other chemicals [127]. The authors list the various constituents of the soy diet but did not mention the amount of genistein, daidzein, or other isoflavones present in each diet [127].…”