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Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast.

Identifieur interne : 001748 ( Main/Exploration ); précédent : 001747; suivant : 001749

Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast.

Auteurs : E B Mougey [États-Unis] ; J E Lang ; X. Wen ; J J Lima

Source :

Journal of clinical pharmacology [ 1552-4604 ] ; 2011.

RBID : pubmed:20974993

English descriptors

KwdEn :
- Acetates (administration & dosage), Acetates (blood), Acetates (pharmacokinetics), Adolescent, Anti-Asthmatic Agents (administration & dosage), Anti-Asthmatic Agents (blood), Anti-Asthmatic Agents (pharmacokinetics), Area Under Curve, Asthma (drug therapy), Asthma (metabolism), Asthma (physiopathology), Beverages, Citrus paradisi, Citrus sinensis, Cross-Over Studies, Female, Florida, Food-Drug Interactions, Fruit, Heterozygote, Homozygote, Humans, Isotonic Solutions, Leukotriene Antagonists (administration & dosage), Leukotriene Antagonists (blood), Leukotriene Antagonists (pharmacokinetics), Male, Models, Biological, Organic Anion Transporters (genetics), Organic Anion Transporters (metabolism), Phenotype, Polymorphism, Genetic, Quinolines (administration & dosage), Quinolines (blood), Quinolines (pharmacokinetics).
MESH :
- chemical , administration & dosage : Acetates, Anti-Asthmatic Agents, Leukotriene Antagonists, Quinolines.
- chemical , blood : Acetates, Anti-Asthmatic Agents, Leukotriene Antagonists, Quinolines.
- chemical , genetics : Organic Anion Transporters.
- chemical , metabolism : Organic Anion Transporters.
- chemical , pharmacokinetics : Acetates, Anti-Asthmatic Agents, Leukotriene Antagonists, Quinolines.
- geographic : Florida, Isotonic Solutions.
- drug therapy : Asthma.
- metabolism : Asthma.
- physiopathology : Asthma.
- Adolescent, Area Under Curve, Beverages, Citrus paradisi, Citrus sinensis, Cross-Over Studies, Female, Food-Drug Interactions, Fruit, Heterozygote, Homozygote, Humans, Male, Models, Biological, Phenotype, Polymorphism, Genetic.

Abstract

Previously the authors found that a common polymorphism, rs12422149 (SLCO2B1{NM_007256.2}:c.935G>A), in the gene coding for OATP2B1, was associated with absorption of and response to montelukast in humans. In vitro studies showed that citrus juice could reduce the permeability of montelukast consistent with known inhibition of organic anion-transporting polypeptides. To study the clinical significance of c.935G>A, the authors conducted a single-dose, pharmacokinetic study of montelukast co-ingested with citrus juice. On average, co-ingestion with either orange juice or 4× concentrated grapefruit juice had a minimal effect on the area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(0→∞)) of montelukast relative to co-ingestion with Gatorade control (n = 24). However when the data were stratified by genotype at c.935 (G/G n = 21, A/G n = 5), a significant reduction in AUC(0→∞) was detected with orange juice in G/G homozygotes (AUC(0→∞), G/G, Gatorade = 2560 ± 900 ng·h·mL(-1) vs AUC(0→∞), G/G, orange juice = 2010 ± 650 ng·h·mL(-1), P = .032). Significantly, A/G heterozygotes showed reduced AUC(0→∞) relative to G/G homozygotes, independent of treatment (AUC(0→∞), G/G, combined treatments = 2310 ± 820 ng·h·mL(-1) vs AUC(0→∞), A/G, combined treatments = 1460 ± 340 ng·h·mL(-1), P = 2.0 × 10(-5)) replicating previous observations.

DOI: 10.1177/0091270010374472
PubMed: 20974993

Affiliations:

Le document en format XML

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<term>Isotonic Solutions</term>
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<front><div type="abstract" xml:lang="en">Previously the authors found that a common polymorphism, rs12422149 (SLCO2B1{NM_007256.2}:c.935G>A), in the gene coding for OATP2B1, was associated with absorption of and response to montelukast in humans. In vitro studies showed that citrus juice could reduce the permeability of montelukast consistent with known inhibition of organic anion-transporting polypeptides. To study the clinical significance of c.935G>A, the authors conducted a single-dose, pharmacokinetic study of montelukast co-ingested with citrus juice. On average, co-ingestion with either orange juice or 4× concentrated grapefruit juice had a minimal effect on the area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(0→∞)) of montelukast relative to co-ingestion with Gatorade control (n = 24). However when the data were stratified by genotype at c.935 (G/G n = 21, A/G n = 5), a significant reduction in AUC(0→∞) was detected with orange juice in G/G homozygotes (AUC(0→∞), G/G, Gatorade = 2560 ± 900 ng·h·mL(-1) vs AUC(0→∞), G/G, orange juice = 2010 ± 650 ng·h·mL(-1), P = .032). Significantly, A/G heterozygotes showed reduced AUC(0→∞) relative to G/G homozygotes, independent of treatment (AUC(0→∞), G/G, combined treatments = 2310 ± 820 ng·h·mL(-1) vs AUC(0→∞), A/G, combined treatments = 1460 ± 340 ng·h·mL(-1), P = 2.0 × 10(-5)) replicating previous observations.</div>
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Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast.

Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast.

Source :

English descriptors

Abstract

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