Table 5.
Comparison of exenatide clearance and dose–weight-normalized AUC0–∞ and Cmax between the renal impairment groups (mild, moderate and ESRD) and the control group using data from multiple trials*
| Pharmacokinetic parameter | Renal function group | n | LS geometric mean | LS geometric mean ratio renal group/normal (90% CI) | P-value |
|---|---|---|---|---|---|
| AUC0–∞ (pg h ml−1)/(µg kg−1) | Normal | 71 | 10 913 | – | – |
| Mild RI | 12 | 12 842 | 1.18 (0.97, 1.42) | 0.156 | |
| Moderate RI | 6 | 17 751 | 1.63 (1.25, 2.12) | 0.003 | |
| ESRD | 8 | 68 054 | 6.24 (4.94, 7.87) | <0.001 | |
| Cmax (pg ml−1)/(µg kg−1) | Normal | 71 | 2 312 | – | – |
| Mild RI | 12 | 2 708 | 1.17 (0.92, 1.49) | 0.284 | |
| Moderate RI | 6 | 3 098 | 1.34 (0.95, 1.89) | 0.160 | |
| ESRD | 8 | 7 595 | 3.28 (2.43, 4.44) | <0.001 | |
| CLp/F (l h−1) | Normal | 71 | 8.14 | – | – |
| Mild RI | 12 | 7.11 | 0.87 (0.69, 1.11) | 0.258 | |
| Moderate RI* | 6 | 5.19 | 0.64 (0.46, 0.89) | 0.008 | |
| ESRD | 8 | 1.3 | 0.16 (0.12, 0.22) | <0.001 |
*
Clearance estimates for subjects with normal renal function were obtained by combining the control group of the renal study and four historical studies in subjects with Type 2 diabetes. ESRD, End-stage renal disease; RI, renal impairment.