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Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers.
Akamine Y
,
Miura M
,
Komori H
,
Saito S
,
Kusuhara H
,
Tamai I
,
Ieiri I
,
Uno T
,
Yasui-Furukori N
.
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PURPOSE: We examined the effect of a single apple juice intake on the pharmacokinetics of fexofenadine enantiomers in healthy Japanese subjects.
METHODS: In a randomized two phase, open-label crossover study, 14 subjects received 60 mg of racemic fexofenadine simultaneously with water or apple juice. For the uptake studies, oocytes expressing organic anion-transporting polypeptide 2B1 (OATP2B1) were incubated with 100 μM (R)- and (S)-fexofenadine in the presence or absence of 10 % apple juice.
RESULTS: One-time ingestion of apple juice significantly decreased the area under the plasma concentration-time curve (AUC0-24) for (R)- and (S)-fexofenadine by 49 and 59 %, respectively, and prolonged the time to reach the maximum plasma concentration (t max) of both enantiomers (P < 0.001). Although apple juice greatly reduced the amount of (R)- and (S)-fexofenadine excretion into urine (Ae0-24) by 54 and 58 %, respectively, the renal clearances of both enantiomers were unchanged between the control and apple juice phases. For in vitro uptake studies, the uptake of both fexofenadine enantiomers into OATP2B1 complementary RNA (cRNA)-injected oocytes was significantly higher than that into water-injected oocytes, and this effect was greater for (R)-fexofenadine. In addition, apple juice significantly decreased the uptake of both enantiomers into OATP2B1 cRNA-injected oocytes.
CONCLUSIONS: These results suggest that OATP2B1 plays an important role in the stereoselective pharmacokinetics of fexofenadine and that one-time apple juice ingestion probably inhibits intestinal OATP2B1-mediated transport of both enantiomers. In addition, this study demonstrates that the OATP2B1 inhibition effect does not require repeated ingestion or a large volume of apple juice.
Akamine,
Influence of drug-transporter polymorphisms on the pharmacokinetics of fexofenadine enantiomers.
2010, Pubmed
Akamine,
Influence of drug-transporter polymorphisms on the pharmacokinetics of fexofenadine enantiomers.
2010,
Pubmed
Akamine,
Carbamazepine differentially affects the pharmacokinetics of fexofenadine enantiomers.
2012,
Pubmed
Bailey,
Fruit juice inhibition of uptake transport: a new type of food-drug interaction.
2010,
Pubmed
Bailey,
Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice.
2007,
Pubmed
Bidstrup,
Rifampicin seems to act as both an inducer and an inhibitor of the metabolism of repaglinide.
2004,
Pubmed
Cvetkovic,
OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine.
1999,
Pubmed
Dresser,
Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine.
2002,
Pubmed
Giacomini,
Membrane transporters in drug development.
2010,
Pubmed
Glaeser,
Intestinal drug transporter expression and the impact of grapefruit juice in humans.
2007,
Pubmed
Imanaga,
The effects of the SLCO2B1 c.1457C > T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans.
2011,
Pubmed
,
Xenbase
Kalliokoski,
Impact of OATP transporters on pharmacokinetics.
2009,
Pubmed
Kusuhara,
Effect of coadministration of single and multiple doses of rifampicin on the pharmacokinetics of fexofenadine enantiomers in healthy subjects.
2013,
Pubmed
Lilja,
Orange juice substantially reduces the bioavailability of the beta-adrenergic-blocking agent celiprolol.
2004,
Pubmed
Lilja,
Effects of orange juice on the pharmacokinetics of atenolol.
2005,
Pubmed
Lilja,
Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol.
2003,
Pubmed
Matsushima,
The inhibition of human multidrug and toxin extrusion 1 is involved in the drug-drug interaction caused by cimetidine.
2009,
Pubmed
Miura,
Determination of fexofenadine enantiomers in human plasma with high-performance liquid chromatography.
2007,
Pubmed
Neuhofel,
Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction.
2002,
Pubmed
Pauli-Magnus,
Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein.
2000,
Pubmed
Rebello,
Intestinal OATP1A2 inhibition as a potential mechanism for the effect of grapefruit juice on aliskiren pharmacokinetics in healthy subjects.
2012,
Pubmed
Robbins,
Dose proportionality and comparison of single and multiple dose pharmacokinetics of fexofenadine (MDL 16455) and its enantiomers in healthy male volunteers.
1998,
Pubmed
Rodríguez-Fragoso,
Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters.
2011,
Pubmed
Sakugawa,
Enantioselective disposition of fexofenadine with the P-glycoprotein inhibitor verapamil.
2009,
Pubmed
Satoh,
Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B.
2005,
Pubmed
Schwarz,
Grapefruit juice ingestion significantly reduces talinolol bioavailability.
2005,
Pubmed
Shirasaka,
Concentration-dependent effect of naringin on intestinal absorption of beta(1)-adrenoceptor antagonist talinolol mediated by p-glycoprotein and organic anion transporting polypeptide (Oatp).
2009,
Pubmed
,
Xenbase
Shirasaka,
Long-lasting inhibitory effect of apple and orange juices, but not grapefruit juice, on OATP2B1-mediated drug absorption.
2013,
Pubmed
Shirasaka,
Major active components in grapefruit, orange, and apple juices responsible for OATP2B1-mediated drug interactions.
2013,
Pubmed
Shitara,
Clinical importance of OATP1B1 and OATP1B3 in drug-drug interactions.
2011,
Pubmed
Tapaninen,
Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren.
2011,
Pubmed
Tateishi,
The different effects of itraconazole on the pharmacokinetics of fexofenadine enantiomers.
2008,
Pubmed
Xiong,
Dual effects of rifampin on the pharmacokinetics of atrasentan.
2007,
Pubmed
Zheng,
Elucidating rifampin's inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers: unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its primary metabolite.
2009,
Pubmed
van Giersbergen,
Inhibitory and inductive effects of rifampin on the pharmacokinetics of bosentan in healthy subjects.
2007,
Pubmed
