Table 1.
Chronic effect of PF-03882845 and eplerenone on UACR and serum K+.
| Compound | Endpoint | EC50 nM (Total conc) | 95% CI lower limit | 95% CI upper limit | fEC50 nM (corrected for for protein binding)a | fEC50/in vitro potencyb | TI (95% CI)c |
|---|---|---|---|---|---|---|---|
| PF-03882845 | Serum K+ | 874 | 75.5 | 1671 | 3.32 | 4.43 | 84.0 |
| UACR | 10.4 | 2.36 | 18.5 | 0.0395 | 0.0527 | (4.1–710) | |
| Eplerenone | Serum K+ | 988 | 134 | 1843 | 672 | 6.16 | 1.47 |
| UACR | 671 | 411 | 932 | 456 | 4.19 | (0.14–4.5) |
Data expressed as EC50 with 95% confidence interval (CI).
a
fEC50: EC50 multiplied by fraction unbound: PF-03882845: 0.0038; Eplerenone: 0.68.
b
In vitro potency: PF-03882845: 0.75 nM; Eplerenone: 109 nM.
c
Therapeutic index (TI) calculated as the ratio of “EC50/in vitro potency” for serum K+ to “EC50/in vitro potency” for UACR.