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Maraviroc is a substrate for OATP1B1 in vitro and maraviroc plasma concentrations are influenced by SLCO1B1 521 T>C polymorphism

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العنوان: Maraviroc is a substrate for OATP1B1 in vitro and maraviroc plasma concentrations are influenced by SLCO1B1 521 T>C polymorphism
المؤلفون: Andrea Calcagno, Antonio D'Avolio, Antonella Castagna, Silvia Nozza, Marco Siccardi, Francesca Romana Stefani, Giovanni Di Perri, David Back, Lorena Baietto, Wai San Kwan, Stefano Bonora, Marco Simiele, Andrew Owen, Darren M. Moss, Adriano Lazzarin
المساهمون: Siccardi, Marco, D'Avolio, Antonio, Nozza, Silvia, Simiele, Marco, Baietto, Lorena, Stefani, Francesca Romana, Moss, Darren, Kwan, Wai san, Castagna, Antonella, Lazzarin, Adriano, Calcagno, Andrea, Bonora, Stefano, Back, David, Di Perri, Giovanni, Owen, Andrew
بيانات النشر: LIPPINCOTT WILLIAMS & WILKINS, 2010.
سنة النشر: 2010
مصطلحات موضوعية: Male, Oocyte, maraviroc, Xenopus laevi, Etravirine, Organic Anion Transporters, Organic Anion Transporter, Pharmacology, Mass Spectrometry, Substrate Specificity, Maraviroc, chemistry.chemical_compound, Xenopus laevis, General Pharmacology, Toxicology and Pharmaceutics, pharmacokinetic, Genetics (clinical), Liver-Specific Organic Anion Transporter 1, Middle Aged, Solute Carrier Organic Anion Transporter Family Member 1b1, pharmacogenetic, Molecular Medicine, Female, medicine.drug, Human, Adult, Efavirenz, Genotype, Reproducibility of Result, Genetic Association Studie, Biology, Polymorphism, Single Nucleotide, uptake transporter, Pharmacokinetics, Genetic, Cyclohexanes, Cyclohexane, Genetics, medicine, Animals, Humans, Molecular Biology, Genetic Association Studies, Dose-Response Relationship, Drug, Animal, Reproducibility of Results, Biological Transport, Odds ratio, Triazoles, In vitro, SLCO1B1, chemistry, biology.protein, Oocytes, Triazole, Pharmacogenetics, Chromatography, Liquid
الوصف: Background: Organic anion transporting polypeptides (OATPs) are emerging as major determinants of pharmacokinetics for numerous drugs, with the 1B1 isoform-mediating hepatic uptake. The 521 T>C polymorphism has been correlated earlier with higher plasma concentrations of several drugs and the aim of this study was to determine whether this polymorphism influences trough concentrations of maraviroc. Methods: The uptake of maraviroc by OATP1B1 was assessed using a heterologous Xenopus laevis oocyte expression system and quantified using a novel liquid chromatography-mass spectrometry method. Regression analyses were conducted to identify factors associated with maraviroc Ctrough in 59 patients treated with maraviroc at 150, 300, or 600 mg twice daily. Results: Maraviroc was identified as a substrate for OATP1B1 with a Km of 33.9 μmol/l. A dose of 600 mg of etravirine or efavirenz [odds ratio (OR)=0.22, 95% confidence interval (95% CI): 0.06-0.76; P=0.016] and SLCO1B1 521 heterozygosity were both associated with maraviroc Ctrough, above the suggested target concentration of 50 ng/ml (OR=20.3, 95% CI: 2.2-182; P=0.007). Conclusion: These findings show the importance of OATP1B1 for variability in maraviroc pharmacokinetics. Furthermore, the SLCO1B1 521 T>C polymorphism maybe useful in predicting higher plasma concentrations but these data should be confirmed before prospective clinical studies to define the clinical usefulness. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
اللغة: English
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6623c27d52b09a7d158f2fa1c2a71acTest
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....d6623c27d52b09a7d158f2fa1c2a71ac
قاعدة البيانات: OpenAIRE
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