Table 7.
Pharmacokinetic differences among dipeptidyl-peptidase-4 inhibitors
| Teneligliptin | Sitagliptin [69] | Vildagliptin [70] | Alogliptin [71] | Linagliptin [72] | Anagliptin [73] | Saxagliptin [74] | Trelagliptin [75] | Omarigliptin [76] | |
|---|---|---|---|---|---|---|---|---|---|
| Standard dosea | Once daily 20 mg | Once daily 50 mg | Twice daily 50 mg | Once daily 25 mg | Once daily 5 mg | Twice daily 100 mg | Once daily 5 mg | Once weekly 100 mg | Once weekly 25 mg |
| Dose increasing | Yes (40 mg) | Yes (100 mg) | No | No | No | Yes (200 mg) | No | No | No |
| Dose adjustment required in patients with renal impairment | No | Yes (12.5, 25 mg) | Yes (50 mg, once daily) | Yes (6.25, 12.5 mg) | No | Yes (once daily, 100 mg) | Yes (2.5 mg) | Yes (50 mg) | Yes (12.5 mg) |
| t½, h [mean (SD)] | 24.2 (5.0) | 11.4 (2.4) | 1.77 (0.23) | 17.1 (2.0) | 105 (8.26) b |
t½,α 2.02 (0.208) t½,β 6.20 (3.11) |
6.47 (0.98) | 54.3 (7.9) | 38.89 (25.78) |
| Excretion | Metabolism/renal excretion | Renal excretion | Metabolism | Renal excretion | Bile excretion | Metabolism/renal excretion | Metabolism/renal excretion | Renal excretion | Renal excretion |
| Metabolic enzyme [77] |
CYP3A4 FMO3 |
Minor CYP3A4 CYP2C8 |
Non-CYP |
Minor CYP2D6 CYP3A4 |
Minor CYP3A4 |
DPP-4, carboxyesterase, cholinesterase | CYP3A4/5 |
Minor CYP2D6 CYP3A4 |
No |
| Renal impairment (AUC) | 1.17- to 1.68-fold | 1.61- to 4.50-fold | 1.31- to 2.33-fold | 1.7- to 3.8-fold [78] | 1.22- to 1.56-fold [79] | 1.65- to 3.22-fold | 1.16- to 2.08-fold [80] | 1.56- to 3.68-fold | 0.94- to 1.97-fold |
| Drug–drug interactions (AUC) | 1.49-fold (ketoconazole) | 1.29-fold (cyclosporine) | 2.01-fold (ritonavir) [81] | 1.81-fold (probenecid) | 2.45-fold (ketoconazole) [82] | ||||
| 0.61-fold (rifampin) [81] |
AUC area under the plasma concentration time-curve, CYP cytochrome P450, FMO3 flavin-containing monooxygenase 3, SD standard deviation, t½ elimination half-life
aApproval dose in Japan
bGeometric mean