Table 1. Pharmacokinetic characteristics of dipeptidyl peptidase-4 inhibitors.
| Drug | Metabolism (%) | Excretion unchanged (%) | Protein binding | Metabolic enzymes | Transporters | In vitro assessment of drug interaction | References |
|---|---|---|---|---|---|---|---|
| Alogliptin | < 7% of alogliptin concentration in urine | 60–70% of administered amount | 20% | CYP2D6/CYP3A4 | Not a substrate of OAT1, OAT3, OCT2 | Not inhibit (at clinically relevant concentration): CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4, CYP2D6/OAT1, OAT3, OCT2; not induce (at clinically relevant concentration): CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4 | [22,23,24] |
| Anagliptin | 29.2% of the administered amount | 46.6% in urine and 4.1% in feces of administered amount | 37.1–48.2% | CYP independent hydrolysis | Substrate of OAT1, OAT3, P-gp, MRP2 (anagliptin), Substrate of OAT3, BCRP, MRP2 and MRP4 (metabolite) | Inhibit: OAT3, OCT2 (in supratherapeutic concentration); not inhibit: CYP1A, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 | [25,26,27] |
| Evogliptin | - | < 25% of administered amount (rat study) | - | CYP3A4 | Substrate of P-gp, BCRP (weak), not a substrate of OAT1B1, OAT1B3, OAT1, OAT3, OCT2 | Not inhibit: CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4/P-gp, BCRP, OAT1B1, OAT1B3, OAT1, OAT3 or OCT2; not induce: CYP1A2, 2B6, 3A4 | [28,30,31,32] |
| Gemigliptin | 30.1–47.6% of plasma radioactivity | 67.2–100% of plasma radioactivity | 20–50% | CYP3A4 | Substrate of P-gp | Inhibit: P-gp (weakly in high concentration); not inhibit: CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4; not induce: CYP1A2, 2C8, 2C9, 2C19, 3A4 | [34,35] |
| Linagliptin | 17.4% in feces and 2.2% in urine of administered amount | 35.8% in feces and 25.3% in urine of administered amount | 75–99% | CYP3A4 | Substrate of P-gp, OCT2, not a substrate of OATP1B1/1B3, OAT1/3/4 and OCT1 | Inhibit: CYP3A4 (weak to moderate)/P-gp (in supratherapeutic concentration), OCT1/2 (substrate specific); not inhibit: CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 4A11/OCT1/2; not induce: CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 4A11 | [36,37,38,39] |
| Saxagliptin | 36% of radioactivity in urine | 24% of radioactivity in urine | 50–75% | CYP3A4/5 | Substrate of P-gp | Not inihibit: CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/P-gp; not induce: CYP1A2, 2B6, 2C8, 2C9, 3A4/P-gp | [40,41] |
| Sitagliptin | 16% of administered amount | 79% of administered amount | 38% | CYP3A4/CYP2C8 | Substrate of P-gp, OAT3 | Not inhibit: CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 or 2B6; not induce: CYP3A4 | [42,43,44,45] |
| Teneligliptin | 66–80% of absorbed teneligliptin | 20–34% of absorbed teneligliptin | 43–74% | CYP3A4, FMO3 | Substrate of P-gycoprotein | Inhibit: CYP2D6, CYP3A4, FMO (weakly)/P-gp and OAT3 (in supratherapeutic concentration); not inhibit: CYP isozyme excluding CYP2D6, 3A4; not induce: CYP3A4, CYP1A2 | [46,47,48,49,50] |
| Vildagliptin | 72.4% of total plasma radioactivity exposure | 23% of administered amount | 85% | CYP independent hydrolysis, UGT2B7, UGT2B17 and UGT2B4 | Substrate of P-gp (weak) | Not inhibit: CYP isoforms; not induce: CYP isoforms | [53,55] |
CYP, cytochrome P450; OAT, organic anion transporter; OCT, organic cation transporter; P-gp, P-glycoprotein; BCRP, breast cancer resistance protein; FMO3, flavin-containing monooxygenase 3; UGT, UDP-glucuronosyltransferase.