European Journal of Clinical Pharmacology

, Volume 69, Issue 7, pp 1401–1409

Effect of ABCB1 polymorphisms and atorvastatin on sitagliptin pharmacokinetics in healthy volunteers

  • Christina L. Aquilante
  • Michael F. Wempe
  • Maha S. Sidhom
  • Lisa A. Kosmiski
  • Julie A. Predhomme
Pharmacogenetics

DOI: 10.1007/s00228-013-1475-y

Cite this article as:
Aquilante, C.L., Wempe, M.F., Sidhom, M.S. et al. Eur J Clin Pharmacol (2013) 69: 1401. doi:10.1007/s00228-013-1475-y

Abstract

Objectives

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.

Keywords

Sitagliptin Atorvastatin ABCB1 P-glycoprotein Pharmacogenetics Pharmacokinetics 

Supplementary material

228_2013_1475_MOESM1_ESM.docx (16 kb)
ESM 1(DOCX 15 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Christina L. Aquilante
    • 1
  • Michael F. Wempe
    • 1
  • Maha S. Sidhom
    • 1
  • Lisa A. Kosmiski
    • 2
  • Julie A. Predhomme
    • 1
  1. 1.Department of Pharmaceutical SciencesUniversity of Colorado Skaggs School of Pharmacy and Pharmaceutical SciencesAuroraUSA
  2. 2.Division of Endocrinology, Diabetes, and MetabolismUniversity of Colorado School of MedicineAuroraUSA