In Vivo Assessment of Drug Interactions

Effects of Alogliptin on the Pharmacokinetics of Other Drugs

In clinical studies, alogliptin did not meaningfully increase the systemic exposure to the following drugs that are metabolized by CYP isozymes or excreted unchanged in urine (Figure 1). No dose adjustment of alogliptin is recommended based on results of the described pharmacokinetic studies.

Figure 1. Effect of Alogliptin on the Pharmacokinetic Exposure to Other Drugs

Figure 1

*Warfarin was given once daily at a stable dose in the range of 1 mg to 10 mg. Alogliptin had no significant effect on the prothrombin time (PT) or International Normalized Ratio (INR).

**Caffeine (1A2 substrate), tolbutamide (2C9 substrate), dextromethorphan (2D6 substrate), midazolam (3A4 substrate) and fexofenadine (P-gp substrate) were administered as a cocktail.

Effects of Other Drugs on the Pharmacokinetics of Alogliptin

There are no clinically meaningful changes in the pharmacokinetics of alogliptin when alogliptin is administered concomitantly with the drugs described below (Figure 2).

Figure 2. Effect of Other Drugs on the Pharmacokinetic Exposure of Alogliptin

Figure 2

Pioglitazone

Table 8. Effect of Pioglitazone Coadministration on Systemic Exposure of Other Drugs
Coadministered Drug
Pioglitazone Dosage Regimen (mg)* Name and Dose Regimens Change in AUC† Change in Cmax†
* Daily for seven days unless otherwise noted † % change (with/without coadministered drug and no change=0%); symbols of ↑ and ↓ indicate the exposure increase and decrease, respectively ‡ Pioglitazone had no clinically significant effect on prothrombin time
45 mg
(N=12) Warfarin‡
Daily loading then maintenance doses based PT and INR values
Quick's Value=35 ± 5% R-Warfarin ↓3% R-Warfarin ↓2%
S-Warfarin ↓1% S-Warfarin ↑1%
45 mg
(N=12) Digoxin
0.200 mg twice daily (loading dose) then 0.250 mg daily (maintenance dose, 7 days) ↑15% ↑17%
45 mg daily for 21 days
(N=35) Oral Contraceptive
[Ethinyl Estradiol (EE) 0.035 mg plus
Norethindrone (NE) 1 mg] for 21 days EE ↓11% EE ↓13%
NE ↑3% NE ↓7%
45 mg
(N=23) Fexofenadine
60 mg twice daily for 7 days ↑30% ↑37%
45 mg
(N=14) Glipizide
5 mg daily for 7 days ↓3% ↓8%
45 mg daily for 8 days
(N=16) Metformin
1000 mg single dose on 8 days ↓3% ↓5%
45 mg
(N=21) Midazolam
7.5 mg single dose on day 15 ↓26% ↓26%
45 mg
(N=24) Ranitidine
150 mg twice daily for 7 days ↑1% ↓1%
45 mg daily for 4 days
(N=24) Nifedipine ER
30 mg daily for 4 days ↓13% ↓17%
45 mg
(N=25) Atorvastatin Ca
80 mg daily for 7 days ↓14% ↓23%
45 mg
(N=22) Theophylline
400 mg twice daily for 7 days ↑2% ↑5%
Table 9. Effect of Coadministered Drugs on P