Effects of vercirnon on the activity of CYP3A4, CYP2C19 and CYP2C8 enzymes and BCRP and OATP1B1 transporters using probe substrates
| العنوان: | Effects of vercirnon on the activity of CYP3A4, CYP2C19 and CYP2C8 enzymes and BCRP and OATP1B1 transporters using probe substrates |
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| المؤلفون: | Lynda J. Haberer, Iain McSherry, Linda McCarthy, Anna Cargill |
| المصدر: | European Journal of Clinical Pharmacology |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Male, CYP2C8, CYP3A4, Midazolam, Drug interaction, Organic Anion Transporters, CYP2C19, Pharmacology, Cytochrome P-450 CYP2C8, Receptors, CCR, Young Adult, medicine, ATP Binding Cassette Transporter, Subfamily G, Member 2, Cytochrome P-450 CYP3A, Humans, Drug Interactions, Pharmacology (medical), Rosuvastatin, Rosuvastatin Calcium, Omeprazole, Sulfonamides, Vercirnon, Pioglitazone, Liver-Specific Organic Anion Transporter 1, Chemistry, OATP1B1, General Medicine, Middle Aged, Clinical Trial, Neoplasm Proteins, Cytochrome P-450 CYP2C19, Fluorobenzenes, Pyrimidines, ATP-Binding Cassette Transporters, Female, Thiazolidinediones, BCRP, Aryl Hydrocarbon Hydroxylases, medicine.drug |
| الوصف: | Purpose Vercirnon is a CCR9 chemokine receptor antagonist being developed for the treatment of Crohn’s disease. As a variety of concomitant medications are often required for the treatment of Crohn’s disease, it is important to characterise the drug interaction profile of vercirnon. To confirm the results of previous in vitro inhibition studies, this study assessed the in vivo effect of vercirnon on the activity of cytochrome P450 enzymes (CYP3A4, CYP2C19 and CYP2C8) and drug transport proteins (BCRP and OATP1B1) using probe substrates. Methods This was an open-label, single-sequence, repeat-dose study conducted in 24 healthy adult subjects. On days 1–4, subjects received probe substrates (midazolam, pioglitazone, omeprazole and rosuvastatin; in that order), followed by administration of vercirnon 500 mg twice daily (BID) on days 5–14. On days 11–14, in addition to vercirnon 500 mg BID, subjects also received probe substrates as on days 1–4. Blood samples were collected for pharmacokinetic analysis of probe substrates, vercirnon and two of its metabolites. Results Geometric least-squares mean ratios (90 % confidence interval) of area under the concentration-time curve from time zero to infinity for probe administered with vercirnon (test) compared with probe alone (reference) for midazolam, pioglitazone, omeprazole and rosuvastatin were 0.92 (0.85, 0.99), 1.01 (0.95, 1.07), 0.99 (0.76,1.31) and 0.98 (0.88, 1.09), respectively. Conclusions Co-administration of probe substrates midazolam, pioglitazone, omeprazole, and rosuvastatin following repeat dosing of vercirnon 500 mg BID demonstrated vercirnon had no clinically significant effect on CYP3A4, CYP2C8, CYP2C19 enzyme activity or BCRP or OATP1B1 transporter activity. Electronic supplementary material The online version of this article (doi:10.1007/s00228-013-1592-7) contains supplementary material, which is available to authorized users. |
| تدمد: | 1432-1041 0031-6970 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24aec583b5a5ec1e91d450b9bd00d22aTest https://doi.org/10.1007/s00228-013-1592-7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....24aec583b5a5ec1e91d450b9bd00d22a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321041 00316970 |
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