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.
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; and 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 five days, with a single 100 mg dose of sitagliptin administered on day 5. A 24 hour pharmacokinetic study followed each sitagliptin dose, and the study phases were separated by a 14-day washout period.
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 GMRs (90% CIs) for sitagliptin Cmax, AUC0-∞, CLR, and fe 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.
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.