Long-lasting inhibitory effect of apple and orange juices, but not grapefruit juice, on OATP2B1-mediated drug absorption.
Identifieur interne : 000E04 ( Main/Merge ); précédent : 000E03; suivant : 000E05Long-lasting inhibitory effect of apple and orange juices, but not grapefruit juice, on OATP2B1-mediated drug absorption.
Auteurs : Yoshiyuki Shirasaka [Japon] ; Megumi Shichiri ; Yukiko Murata ; Takanori Mori ; Takeo Nakanishi ; Ikumi TamaiSource :
- Drug metabolism and disposition: the biological fate of chemicals [ 1521-009X ] ; 2013.
English descriptors
- KwdEn :
- Absorption, Animals, Beverages, Binding Sites, Binding, Competitive, Biological Transport, Citrus paradisi, Citrus sinensis, Estrone (analogs & derivatives), Estrone (metabolism), Food-Drug Interactions, Fruit, Kinetics, Malus, Oocytes, Organic Anion Transporters (antagonists & inhibitors), Organic Anion Transporters (genetics), Organic Anion Transporters (metabolism), Terfenadine (analogs & derivatives), Terfenadine (metabolism), Xenopus laevis.
- MESH :
- chemical , analogs & derivatives : Estrone, Terfenadine.
- chemical , antagonists & inhibitors : Organic Anion Transporters.
- chemical , genetics : Organic Anion Transporters.
- chemical , metabolism : Estrone, Organic Anion Transporters, Terfenadine.
- Absorption, Animals, Beverages, Binding Sites, Binding, Competitive, Biological Transport, Citrus paradisi, Citrus sinensis, Food-Drug Interactions, Fruit, Kinetics, Malus, Oocytes, Xenopus laevis.
Abstract
Enzyme-based grapefruit juice (GFJ)-drug interactions are mainly due to mechanism-based irreversible inhibition of metabolizing enzyme CYP3A4 by GFJ components, but the transporter organic anion transporting polypeptide (OATP)2B1 is also a putative site of interaction between drugs and fruit juices (FJ) in the absorption process. Here we aimed to investigate the effect of preincubation with FJ on OATP2B1-mediated transport of drugs in vitro. When OATP2B1-expressing Xenopus oocytes were preincubated with GFJ, orange juice (OJ), or apple juice (AJ), AJ induced a remarkable decrease in OATP2B1-mediated estrone-3-sulfate uptake in a concentration-dependent manner (IC(50) = 1.5%). A similar but less potent effect was observed with OJ (IC(50) = 21%), whereas GFJ had no effect. Similar results were obtained in preincubation studies using fexofenadine. Preincubation with OJ and AJ resulted in time-dependent inhibition of OATP2B1. Again, AJ had the more potent effect; its action lasted for at least 240 minutes, suggesting that AJ irreversibly inhibits OATP2B1-mediated drug uptake. Kinetic analysis revealed that coincubation and preincubation with AJ reduced OATP2B1-mediated estrone-3-sulfate uptake via competitive and noncompetitive mechanisms, respectively. Thus, OATP2B1 is functionally impaired through both competitive and long-lasting inhibition mechanisms by AJ and OJ, but not GFJ. Interestingly, although GFJ but not AJ is able to irreversibly inhibit CYP3A4, in the case of OATP2B1, AJ but not GFJ has a long-lasting inhibitory effect. Accordingly, complex FJ-drug interactions may occur in vivo, and their clinical significance should be examined.
DOI: 10.1124/dmd.112.049635
PubMed: 23264447
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Long-lasting inhibitory effect of apple and orange juices, but not grapefruit juice, on OATP2B1-mediated drug absorption.</title><author><name sortKey="Shirasaka, Yoshiyuki" sort="Shirasaka, Yoshiyuki" uniqKey="Shirasaka Y" first="Yoshiyuki" last="Shirasaka">Yoshiyuki Shirasaka</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192</wicri:regionArea><wicri:noRegion>Kanazawa 920-1192</wicri:noRegion></affiliation></author><author><name sortKey="Shichiri, Megumi" sort="Shichiri, Megumi" uniqKey="Shichiri M" first="Megumi" last="Shichiri">Megumi Shichiri</name></author><author><name sortKey="Murata, Yukiko" sort="Murata, Yukiko" uniqKey="Murata Y" first="Yukiko" last="Murata">Yukiko Murata</name></author><author><name sortKey="Mori, Takanori" sort="Mori, Takanori" uniqKey="Mori T" first="Takanori" last="Mori">Takanori Mori</name></author><author><name sortKey="Nakanishi, Takeo" sort="Nakanishi, Takeo" uniqKey="Nakanishi T" first="Takeo" last="Nakanishi">Takeo Nakanishi</name></author><author><name sortKey="Tamai, Ikumi" sort="Tamai, Ikumi" uniqKey="Tamai I" first="Ikumi" last="Tamai">Ikumi Tamai</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:23264447</idno><idno type="pmid">23264447</idno><idno type="doi">10.1124/dmd.112.049635</idno><idno type="wicri:Area/PubMed/Corpus">000481</idno><idno type="wicri:Area/PubMed/Curation">000481</idno><idno type="wicri:Area/PubMed/Checkpoint">000481</idno><idno type="wicri:Area/Ncbi/Merge">001181</idno><idno 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sortKey="Shichiri, Megumi" sort="Shichiri, Megumi" uniqKey="Shichiri M" first="Megumi" last="Shichiri">Megumi Shichiri</name></author><author><name sortKey="Murata, Yukiko" sort="Murata, Yukiko" uniqKey="Murata Y" first="Yukiko" last="Murata">Yukiko Murata</name></author><author><name sortKey="Mori, Takanori" sort="Mori, Takanori" uniqKey="Mori T" first="Takanori" last="Mori">Takanori Mori</name></author><author><name sortKey="Nakanishi, Takeo" sort="Nakanishi, Takeo" uniqKey="Nakanishi T" first="Takeo" last="Nakanishi">Takeo Nakanishi</name></author><author><name sortKey="Tamai, Ikumi" sort="Tamai, Ikumi" uniqKey="Tamai I" first="Ikumi" last="Tamai">Ikumi Tamai</name></author></analytic><series><title level="j">Drug metabolism and disposition: the biological fate of chemicals</title><idno type="eISSN">1521-009X</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Absorption</term><term>Animals</term><term>Beverages</term><term>Binding Sites</term><term>Binding, Competitive</term><term>Biological Transport</term><term>Citrus paradisi</term><term>Citrus sinensis</term><term>Estrone (analogs & derivatives)</term><term>Estrone (metabolism)</term><term>Food-Drug Interactions</term><term>Fruit</term><term>Kinetics</term><term>Malus</term><term>Oocytes</term><term>Organic Anion Transporters (antagonists & inhibitors)</term><term>Organic Anion Transporters (genetics)</term><term>Organic Anion Transporters (metabolism)</term><term>Terfenadine (analogs & derivatives)</term><term>Terfenadine (metabolism)</term><term>Xenopus laevis</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Estrone</term><term>Terfenadine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Organic Anion Transporters</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Organic Anion Transporters</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Estrone</term><term>Organic Anion Transporters</term><term>Terfenadine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Absorption</term><term>Animals</term><term>Beverages</term><term>Binding Sites</term><term>Binding, Competitive</term><term>Biological Transport</term><term>Citrus paradisi</term><term>Citrus sinensis</term><term>Food-Drug Interactions</term><term>Fruit</term><term>Kinetics</term><term>Malus</term><term>Oocytes</term><term>Xenopus laevis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Enzyme-based grapefruit juice (GFJ)-drug interactions are mainly due to mechanism-based irreversible inhibition of metabolizing enzyme CYP3A4 by GFJ components, but the transporter organic anion transporting polypeptide (OATP)2B1 is also a putative site of interaction between drugs and fruit juices (FJ) in the absorption process. Here we aimed to investigate the effect of preincubation with FJ on OATP2B1-mediated transport of drugs in vitro. When OATP2B1-expressing Xenopus oocytes were preincubated with GFJ, orange juice (OJ), or apple juice (AJ), AJ induced a remarkable decrease in OATP2B1-mediated estrone-3-sulfate uptake in a concentration-dependent manner (IC(50) = 1.5%). A similar but less potent effect was observed with OJ (IC(50) = 21%), whereas GFJ had no effect. Similar results were obtained in preincubation studies using fexofenadine. Preincubation with OJ and AJ resulted in time-dependent inhibition of OATP2B1. Again, AJ had the more potent effect; its action lasted for at least 240 minutes, suggesting that AJ irreversibly inhibits OATP2B1-mediated drug uptake. Kinetic analysis revealed that coincubation and preincubation with AJ reduced OATP2B1-mediated estrone-3-sulfate uptake via competitive and noncompetitive mechanisms, respectively. Thus, OATP2B1 is functionally impaired through both competitive and long-lasting inhibition mechanisms by AJ and OJ, but not GFJ. Interestingly, although GFJ but not AJ is able to irreversibly inhibit CYP3A4, in the case of OATP2B1, AJ but not GFJ has a long-lasting inhibitory effect. Accordingly, complex FJ-drug interactions may occur in vivo, and their clinical significance should be examined.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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