Comparison of the In Vitro IC50 to Inhibit TNF Release in LPS-Stimulated Whole Blood With the Magnitude of Inhibition of TNF In Vivo for Each Subject
| Subject No. . | IC50 (ng/mL) In Vitro . | Inhibition of TNFα Release In Vivo (%) . | Cmax(ng/mL) in Serum . | Tmax (h) . |
|---|---|---|---|---|
| 1 | 675.2 | 14 | 954 | 1.0 |
| 2 | 493.4 | 95 | 360 | 1.33 |
| 3 | 470.3 | 74 | 1,032 | 0.75 |
| 4 | 605.3 | 63 | 944 | 1.0 |
| 5 | 352.3 | 72 | 605 | 0.75 |
| 6 | 557.1 | 94 | 1,065 | 0.50 |
| Subject No. . | IC50 (ng/mL) In Vitro . | Inhibition of TNFα Release In Vivo (%) . | Cmax(ng/mL) in Serum . | Tmax (h) . |
|---|---|---|---|---|
| 1 | 675.2 | 14 | 954 | 1.0 |
| 2 | 493.4 | 95 | 360 | 1.33 |
| 3 | 470.3 | 74 | 1,032 | 0.75 |
| 4 | 605.3 | 63 | 944 | 1.0 |
| 5 | 352.3 | 72 | 605 | 0.75 |
| 6 | 557.1 | 94 | 1,065 | 0.50 |
The peak serum concentrations of GI5402 (Cmax) and time to peak concentration (tmax) are also shown. The in vitro IC50 was determined in whole blood from each subject stimulated with LPS (10 ng/mL) for 24 hours at 37°C in the presence of increasing concentrations of GI5402. Percentage inhibition of in vivo TNFα release by GI5402 is expressed relative to LPS-induced TNFα release in the placebo period (area under the curve). The area was calculated from timepoint −0.5 hours up to the point at which the second derivative of the curve changes sign (5 hours in all subjects). Pearson’s correlation test calculated r2 = .36 and P = .2. For definitions of Cmax and tmax, see Materials and Methods.