In an open-label, two-way crossover randomized study in 12 healthy male volunteers, subjects received 3 days of ritonavir (200 mg twice daily) and a single oral dose of linagliptin (5 mg) on the first day. Following a washout period of at least 35 days, subjects received a single dose of linagliptin (5 mg) as control treatment. In combination with ritonavir, linagliptin tmax was reduced while Cmax and AUC24 were increased approximately 3-fold and 2-fold, respectively. Simulations of steady-state plasma concentrations of linagliptin with or without ritonavir predicted that the increased linagliptin exposure in combination with ritonavir would not result in increased linagliptin accumulation. The increased exposure of linagliptin when coadministered with ritonavir is not considered clinically meaningful based on the large safety window.