title: SLCO2B1 c.935G>A single nucleotide polymorphism has no effect on the pharmacokinetics of montelukast and aliskiren.
abstract: OBJECTIVE
  A nonsynonymous single nucleotide polymorphism (SNP) in the SLCO2B1 gene encoding organic anion transporting polypeptide 2B1 (OATP2B1), c.935G>A (p.R312Q; rs12422149), has been associated with reduced plasma concentrations of montelukast in patients with asthma. Our aim was to examine the possible effects of the SLCO2B1 c.935G>A SNP on the single-dose pharmacokinetics of the suggested OATP2B1 substrates montelukast and aliskiren.
  
  
  METHODS
  Sixteen healthy volunteers with the SLCO2B1 c.935GG genotype, 12 with the c.935GA genotype, and five with the c.935AA genotype ingested a single 10 mg dose of montelukast or a 150 mg dose of aliskiren, with a washout period of 1 week. Plasma montelukast concentrations were measured up to 24 h. Plasma and urine aliskiren concentrations were measured up to 72 and 12 h, respectively, and plasma renin activity up to 24 h after aliskiren intake.
  
  
  RESULTS
  The SLCO2B1 genotypes had no significant effect on the pharmacokinetics of montelukast or aliskiren. The geometric mean ratios with 90% confidence intervals of montelukast area under the plasma concentration-time curve from 0 h to infinity (AUC(0-∞)) in participants with the c.935GA or the c.935AA genotype to those with the c.935GG genotype were 1.02 (0.87, 1.21) or 0.88 (0.71, 1.10), respectively (P=0.557). The geometric mean ratios (90% confidence interval) of aliskiren AUC(0-∞) in participants with the c.935GA or the c.935AA genotype to those with the c.935GG genotype were 0.98 (0.74, 1.30) or 1.24 (0.85, 1.80), respectively (P=0.576).
  
  
  CONCLUSIONS
  These data do not support the suggested functional significance of the SLCO2B1 c.935G>A SNP on OATP2B1 activity in vivo.
authors.affiliation: Department of Clinical Pharmacology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Tuija
authors.initials: T
authors.lastname: Tapaninen
authors.forename: Tiina
authors.initials: T
authors.lastname: Karonen
authors.forename: Janne T
authors.initials: JT
authors.lastname: Backman
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: Mikko
authors.initials: M
authors.lastname: Niemi
mesh_terms: D000085:Acetates / Q000493:pharmacokinetics* / Q000494:pharmacology; D000328:Adult; D000577:Amides / Q000493:pharmacokinetics* / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D003521:Cyclopropanes; D005260:Female; D005650:Fumarates / Q000493:pharmacokinetics* / Q000494:pharmacology; D005838:Genotype; D006801:Humans; D020024:Leukotriene Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011804:Quinolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D011863:Radioimmunoassay; D012083:Renin / Q000378:metabolism; D013440:Sulfides; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D055815:Young Adult; D000092502:Renin Inhibitors
chemical_list: D000085:Acetates; D000577:Amides; D000959:Antihypertensive Agents; D003521:Cyclopropanes; D005650:Fumarates; D020024:Leukotriene Antagonists; D027361:Organic Anion Transporters; D011804:Quinolines; D012083:Renin; D013440:Sulfides; D000092502:Renin Inhibitors; C450859:SLCO2B1 protein, human; C446481:aliskiren; C093875:montelukast