title: Effect of ABCB1 polymorphisms and atorvastatin on sitagliptin pharmacokinetics in healthy volunteers.
abstract: OBJECTIVE
  The objectives of this study were to determine if ABCB1 polymorphisms are associated with interindividual variability in sitagliptin pharmacokinetics and if atorvastatin alters the pharmacokinetic disposition of sitagliptin in healthy volunteers.
  
  
  METHODS
  In this open-label, randomized, two-phase crossover study, healthy volunteers were prospectively stratified according to ABCB1 1236/2677/3435 diplotype (n = 9, CGC/CGC; n = 10, CGC/TTT; n = 10, TTT/TTT). In one phase, participants received a single 100 mg dose of sitagliptin; in the other phase, participants received 40 mg of atorvastatin for 5 days, with a single 100 mg dose of sitagliptin administered on day 5. A 24-h pharmacokinetic study followed each sitagliptin dose, and the study phases were separated by a 14-day washout period.
  
  
  RESULTS
  Sitagliptin pharmacokinetic parameters did not differ significantly between ABCB1 CGC/CGC, CGC/TTT, and TTT/TTT diplotype groups during the monotherapy phase. Atorvastatin administration did not significantly affect sitagliptin pharmacokinetics, with geometric mean ratios (90 % confidence intervals) for sitagliptin maximum plasma concentration, plasma concentration-time curve from zero to infinity, renal clearance, and fraction of sitagliptin excreted unchanged in the urine of 0.93 (0.86-1.01), 0.96 (0.91-1.01), 1.02 (0.93-1.12), and 0.98 (0.90-1.06), respectively.
  
  
  CONCLUSIONS
  ABCB1 CGC/CGC, CGC/TTT, and TTT/TTT diplotypes did not influence sitagliptin pharmacokinetics in healthy volunteers. Furthermore, atorvastatin had no effect on the pharmacokinetics of sitagliptin in the setting of ABCB1 CGC/CGC, CGC/TTT, and TTT/TTT diplotypes.
authors: Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, 12850 East Montview Boulevard, Mail Stop C238, Aurora, CO 80045, USA. Christina.aquilante@ucdenver.edu
authors: Christina L
authors: CL
authors: Aquilante
authors: Michael F
authors: MF
authors: Wempe
authors: Maha S
authors: MS
authors: Sidhom
authors: Lisa A
authors: LA
authors: Kosmiski
authors: Julie A
authors: JA
authors: Predhomme
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000069059:Atorvastatin; D001711:Biotransformation / Q000187:drug effects; D015331:Cohort Studies; D003120:Colorado; D018592:Cross-Over Studies; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004347:Drug Interactions; D005260:Female; D056726:Genetic Association Studies; D006207:Half-Life; D006538:Heptanoic Acids / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011719:Pyrazines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011758:Pyrroles / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011719:Pyrazines; D011758:Pyrroles; D014230:Triazoles; D000069059:Atorvastatin; D000068900:Sitagliptin Phosphate