ABCB1 and SLCO1B3 Gene Polymorphisms and Their Impact on Digoxin Pharmacokinetics in Atrial Fibrillation Patients among the Tunisian Population
| Autor: | Ilhem Hellara, Semir Nouira, Emna Kerkeni, Wahiba Douki, Adel Sekma, Malek Mzali, Kamel Monastiri, Nejia Tounsi, Mohamed Habib Grissa, Nizar Fredj, Imen Trabelsi |
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| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
Organic anion transporter 1 Digoxin Single-nucleotide polymorphism ATP-binding cassette transporter 030204 cardiovascular system & hematology Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine Genotype polycyclic compounds medicine cardiovascular diseases biology business.industry digestive oral and skin physiology Atrial fibrillation General Medicine medicine.disease carbohydrates (lipids) Organic anion-transporting polypeptide Endocrinology biology.protein business medicine.drug |
| Zdroj: | Pharmacology. 99:250-258 |
| ISSN: | 1423-0313 0031-7012 |
| Popis: | Background: Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. Genetic polymorphisms in both genes may explain inter-individual variability of serum digoxin concentration (SDC). This study evaluates the possible effect of the most common ABCB1 and SLCO1B3 polymorphisms on SDC after a single oral dose of digoxin in Tunisian atrial fibrillation (AF) patients. Methods:ABCB1 and SLCO1B3 genotypes were analyzed in 102 patients with AF who received digoxin (0.5 mg) without (group I, n = 58) or with the co-administration of P-gp inhibitors (group II, n = 44). SDCs were determined at 6 h following the oral dose. Results: SDCs levels were significantly higher in patients who were co-administered P-gp inhibitors. No influence was noted in ABCB1 and SLCO1B3 polymorphisms on SDC in group I patients. However, SDCs values were significantly different among ABCB1 single nucleotide polymorphisms (SNPs) genotypes of 2677G>T/A (TT, GG>GT, p < 0.05) and 3435C>T (TT, CC>CT, p < 0.05) only in group II with no effect of 1236C>T and SLCO1B3 SNPs. Conclusion: Results suggest that P-gp inhibitors and ABCB1 gene polymorphisms may affect digoxin pharmacokinetics. |
| Databáze: | OpenAIRE |
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