title: ABCB1 and SLCO1B3 Gene Polymorphisms and Their Impact on Digoxin Pharmacokinetics in Atrial Fibrillation Patients among the Tunisian Population.
abstract: 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.
  
  
  CONCLUSIONS
  Results suggest that P-gp inhibitors and ABCB1 gene polymorphisms may affect digoxin pharmacokinetics.
authors.affiliation: Research Laboratory (LR12SP18), University of Monastir, Monastir, Tunisia.
authors.forename: Nejia
authors.initials: N
authors.lastname: Tounsi
authors.forename: Imen
authors.initials: I
authors.lastname: Trabelsi
authors.forename: Emna
authors.initials: E
authors.lastname: Kerkeni
authors.forename: Mohamed Habib
authors.initials: MH
authors.lastname: Grissa
authors.forename: Nizar
authors.initials: N
authors.lastname: Fredj
authors.forename: Adel
authors.initials: A
authors.lastname: Sekma
authors.forename: Malek
authors.initials: M
authors.lastname: Mzali
authors.forename: Ilhem
authors.initials: I
authors.lastname: Hellara
authors.forename: Kamel
authors.initials: K
authors.lastname: Monastiri
authors.forename: Wahiba
authors.initials: W
authors.lastname: Douki
authors.forename: Semir
authors.initials: S
authors.lastname: Nouira
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000378:metabolism*; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D014416:Tunisia
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D029362:Organic Anion Transporters, Sodium-Independent; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D004077:Digoxin