Effects of the Flavonoid Chrysin on Nitrofurantoin Pharmacokinetics in Rats: Potential Involvement of ABCG2

Wang, Xiaodong; Morris, Marilyn E.

doi:10.1124/dmd.106.011684

Cited by 85 publications

(68 citation statements)

References 34 publications

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“…The mechanisms underlying most of these interactions are effects (inhibition/ induction) on drug metabolizing enzymes and/or efflux drug transporters, such as P-glycoprotein and BCRP (11)(12)(13). Limited information is available concerning interactions between flavonoids and uptake transporters.…”

Section: Discussionmentioning

confidence: 99%

“…These interactions, in some cases, can cause serious or life-threatening adverse effects, especially when flavonoids are used together with narrow therapeutic index drugs (12). On the other hand, flavonoids have been shown to be able to improve the bioavailability of the coadministered drugs, resulting in beneficial flavonoid-drug interactions (11,13). The mechanisms underlying these flavonoid-drug interactions are presumably due to the inhibition of drug metabolizing enzymes and efflux drug transporters, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, flavonoids have been shown to be able to improve the bioavailability of the coadministered drugs, resulting in beneficial flavonoid-drug interactions (11,13). The mechanisms underlying these flavonoid-drug interactions are presumably due to the inhibition of drug metabolizing enzymes and efflux drug transporters, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) (11)(12)(13). However, far less information is available on flavonoid-drug interactions involving uptake transporters, including the monocarboxylate transporters.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic Interaction between the Flavonoid Luteolin and γ-Hydroxybutyrate in Rats: Potential Involvement of Monocarboxylate Transporters

Wang

Morris

2008

AAPS J

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Abstract. Monocarboxylate transporter 1 (MCT1) has been previously reported as an important determinant of the renal reabsorption of the drug of abuse, γ-hydroxybutyrate (GHB). Luteolin is a potent MCT1 inhibitor, inhibiting the uptake of GHB with an IC 50 of 0.41 μM in MCT1-transfected MDA-MB231 cells. The objectives of this study were to characterize the effects of luteolin on GHB pharmacokinetics and pharmacodynamics in rats, and to investigate the mechanism of the interaction using model-fitting methods. GHB (400 and 1,000 mg/kg) and luteolin (0, 4 and 10 mg/kg) were administered to rats via iv bolus doses. The plasma or urine concentrations of luteolin and GHB were determined by HPLC and LC/MS/MS, respectively. The pharmacodynamic parameter sleep time in rats after GHB administration was recorded. A pharmacokinetic model containing capacity-limited renal reabsorption and metabolic clearance was constructed to characterize the in vivo interaction. Luteolin significantly decreased the plasma concentration and AUC, and increased the total and renal clearances of GHB. Moreover, luteolin significantly shortened the duration of GHB (1,000 mg/kg)-induced sleep in rats (161±16, 131±14 and 121±5 min for control, luteolin 4 and 10 mg/kg groups, respectively, p<0.01). An uncompetitive inhibition model, with an inhibition constant of 1.1 μM, best described the in vivo pharmacokinetic interaction. The results of this study indicated that luteolin significantly altered the pharmacokinetics of GHB by inhibiting its MCT1-mediated transport. The interaction between luteolin and GHB may offer a potential clinical detoxification strategy to treat GHB overdoses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic Interaction between the Flavonoid Luteolin and γ-Hydroxybutyrate in Rats: Potential Involvement of Monocarboxylate Transporters

Wang

Morris

2008

AAPS J

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“…Due to its expression in organs important for drug absorption (small intestine), distribution (blood-brain barrier, placenta) and elimination (liver, kidney), BCRP is important not only in MDR but also in drug disposition. BCRP has been reported to play an important role in the disposition of several clinically widely-used drugs, such as topotecan [9], nitrofurantoin [10], fluoroquinolone antibiotics [11] and pitavastatin [12]. For example, Jonker et al [9] investigated the role of BCRP in topotecan disposition and found that the bioavailability of topotecan in plasma was dramatically increased in P-gp-deficient mice (greater than six-fold) when co-administered with GF120918 (a BCRP and P-gp inhibitor), compared with control mice receiving only topotecan.…”

Section: Introductionmentioning

confidence: 99%

Effects of the isoflavonoid biochanin A on the transport of mitoxantrone in vitro and in vivo

Morris

2010

Biopharm & Drug Disp

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The aim of our study was to investigate the effect of biochanin A on the accumulation and transport of mitoxantrone in breast cancer resistance protein (BCRP)-expressing normal cells and its impact on the pharmacokinetics (PK) and tissue distribution of mitoxantrone. In accumulation studies, the intracellular level of mitoxantrone was significantly increased in the presence of 2.5 or 25 microM of biochanin A in both murine and human BCRP-expressing Madin-Darby canine kidney (MDCK) cells, with no effect in corresponding MDCK/Mock cells. In bi-directional transport studies, the P(app,B-A) value of mitoxantrone with biochanin A co-treatment was much lower (6.66+/-0.84x10(-7) cm/s) than that in the absence of biochanin A (21.4+/-4.14x10(-7) cm/s), indicating inhibition of Bcrp1-mediated efflux. To evaluate whether our in vitro results might translate into an in vivo interaction, mitoxantrone PK and tissue distribution, with and without co-administration of biochanin A, was investigated. In contrast to our in vitro results, biochanin A (10 mg/kg, i.v.) had no impact on the concentration of mitoxantrone in plasma and most tissues collected (brain, heart, liver and lung). Surprisingly, the concentrations of mitoxantrone in spleen and kidney were even decreased when biochanin A was co-administered. Interestingly, it was found that the intracellular fluorescence of mitoxantrone was decreased 31.9% when co-incubated with 10 microM biochanin A in P-glycoprotein (P-gp) expressing MCF-7/ADR cells, indicating potential P-gp stimulation. The species difference of the inhibitory effect of biochanin A on BCRP, the extensive metabolism of biochanin A, as well as the stimulation effect of biochanin A on P-gp, may contribute to this in vitro-in vivo disconnect.

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“…In addition, Bcrp1 plays a predominant role in the hepatobiliary excretion of NFT (13,18). Inhibition by isoflavones of bile excretion of NTF was shown since NTF levels in bile were significantly decreased by isoflavone administration: 8.8±3.4 μg/ml in wild-type (NTF, control) vs 3.7±3.3 μg/ml in wild-type mice (NTF+Gen-Daid), p≤0.05 (Fig.…”

Section: Effects Of Genistein and Daidzein On In Vitro Transport Of Nmentioning

confidence: 82%

In Vivo Inhibition of BCRP/ABCG2 Mediated Transport of Nitrofurantoin by the Isoflavones Genistein and Daidzein: A Comparative Study in Bcrp1 −/− Mice

et al. 2010

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Effects of the Flavonoid Chrysin on Nitrofurantoin Pharmacokinetics in Rats: Potential Involvement of ABCG2

Cited by 85 publications

References 34 publications

Pharmacokinetic Interaction between the Flavonoid Luteolin and γ-Hydroxybutyrate in Rats: Potential Involvement of Monocarboxylate Transporters

Pharmacokinetic Interaction between the Flavonoid Luteolin and γ-Hydroxybutyrate in Rats: Potential Involvement of Monocarboxylate Transporters

Effects of the isoflavonoid biochanin A on the transport of mitoxantrone in vitro and in vivo

In Vivo Inhibition of BCRP/ABCG2 Mediated Transport of Nitrofurantoin by the Isoflavones Genistein and Daidzein: A Comparative Study in Bcrp1 −/− Mice

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