TABLE 4.
Summary statistics for total ertapenem single- and multiple-dose PK parameters in plasma by treatment groupd,e
| PK parameter (units) | WCK 6777 2 g | ERT 2 g | WCK 6777 4 g | ERT 3 g | WCK 6777 6 g |
|---|---|---|---|---|---|
| Total ertapenem single-dose PK parameters | |||||
| Cmax (µg/mL) | 196.66 (14) | 303.43 (9) | 354.41 (8) | 378.71 (10) | 391.87 (13) |
| Cmin (µg/mL) | 2.15 (50) | 2.61 (107) | 3.10 (60) | 7.32 (14) | 5.91 (33) |
| Tmax (h) | 0.50 (0.50–0.50) | 1.00 (1.00–1.07) | 1.00 (1.00–1.00) | 2.02 (2.00–2.03) | 2.03 (2.02–2.03) |
| Tmin (h) | 23.60 (23.60–23.70) | 23.65 (23.60–23.70) | 23.60 (23.60–23.60) | 23.60 (23.40–23.60) | 23.60 (23.60–23.70) |
| AUC(0–t) (µg h/mL) | 723.48 (9) | 1,241.47 (18) | 1,377.99 (14) | 2,148.23 (11) | 2,024.46 (10) |
| AUC(0–inf) (µg h/mL) | 742.95 (10) | 1,265.39 (19) | 1,404.86 (15) | 2,199.93 (11) | 2,065.37 (11) |
| AUC(0–24) (µg h/mL) | 728.97 (9) | 1,249.60 (18) | 1,386.28 (14) | 2,156.38 (11) | 2,029.12 (10) |
| AUC(0–last) (µg h/mL) | 728.18 (9) | 1,247.86 (18) | 1,384.69 (14) | 2,153.20 (11) | 2,027.57 (10) |
| t1/2 (h) | 4.34 (12) | 3.76 (22) | 3.92 (14) | 4.20 (4) | 4.20 (10) |
| CLT (L/h) | 1.34 (10) | 1.58 (19) | 1.42 (15) | 1.37 (11) | 1.45 (11) |
| ke (1/h) | 0.16 (12) | 0.18 (22) | 0.18 (14) | 0.17 (4) | 0.17 (10) |
| Vd (L) | 8.43 (7) | 8.57 (9) | 8.04 (12) | 8.28 (10) | 8.81 (13) |
| Total ertapenem multiple-dose PK parameters | |||||
| Cmax,ss (µg/mL) | 181.90 (11) | 341.92 (10) | 344.89 (10) | 387.57 (9) | 343.24 (13) |
| Cmax,ss/dose ([µg/mL]/mg) | 0.18 (11) | 0.17 (10) | 0.17 (10) | 0.13 (9) | 0.11 (13) |
| Cmin,ss (µg/mL) | 1.75 (30) | 1.81 (114) | 1.74 (75) | 4.93 (2) | 3.49 (65) |
| Cavg,ss (µg/mL) | 29.99 (9) | 51.20 (13) | 51.40 (16) | 80.91 (6) | 71.98 (14) |
| Cτ,ss (µg/mL) | 1.75 (30) | 1.85 (111) | 1.74 (75) | 4.93 (2) | 3.50 (64) |
| Tmax,ss (h) | 0.52 (0.50–0.60) | 1.00 (1.00–1.00) | 1.02 (1.00–1.02) | 2.02 (2.02–2.02) | 2.07 (2.02–2.23) |
| Tmin (h) | 24.00 (24.00–24.00) | 24.05 (24.00–24.30) | 24.00 (24.00–24.00) | 24.00 (24.00–24.00) | 24.00 (24.00–24.10) |
| AUC(0–24),ss (µg h/mL) | 719.86 (9) | 1,228.88 (14) | 1,233.66 (16) | 1,940.84 (6) | 1,726.43 (14) |
| AUC(0–τ),ss (µg h/mL) | 719.86 (9) | 1,228.88 (14) | 1,233.66 (16) | 1,940.84 (6) | 1,726.43 (14) |
| AUC(0–τ),ss/dose ([µg h/mL]/mg) | 0.72 (9) | 0.61 (13) | 0.62 (16) | 0.65 (6) | 0.58 (14) |
| t1/2 (h) | 3.91 (8) | 3.64 (19) | 3.67 (21) | 4.14 (4) | 3.86 (18) |
| CLT (L/h) | 1.39 (9) | 1.63 (13) | 1.62 (16) | 1.55 (7) | 1.74 (14) |
| Vd,ss (L) | 6.86 (5) | 6.73 (11) | 6.51 (11) | 7.17 (9) | 7.58 (10) |
| Linearity indexa | 0.97 (4) | 0.97 (7) | 0.88 (11) | 0.89 (6) | 0.84 (9) |
| RAUCb | 0.99 (5) | 0.98 (7) | 0.89 (11) | 0.91 (6) | 0.85 (9) |
| RCmaxc | 0.92 (17) | 1.13 (14) | 0.97 (7) | 1.01 (8) | 0.88 (8) |
Linearity index is defined as AUC(0–τ),ss (Dose 7)/AUC(0–inf) (Dose 1).
RAUC is defined as AUC(0–τ) (Dose 7)/AUC(0–24) (Dose 1).
RCmax is defined as Cmax (Dose 7)/Cmax (Dose 1).
Single-dose parameters are calculated over the 24-h period following Dose 1. Multi-dose parameters are calculated over the 24-h period following Dose 7. For this study, the dosing interval (τ) was 24 h; therefore, AUC(0–24),ss and AUC(0–τ),ss are numerically identical, and Cτ,ss represents the concentration at the end of the dosing interval (equivalent to Cmin,ss). Values of GM (CV%) are shown, except for Tmax and Tmin, for which values of median (min-max) are shown.
AUC, area under the concentration-time curve; Cavg, average concentration; CLT, total clearance; Cmax, maximum concentration; Cmin, minimum concentration; CV, coefficient of variation; ERT, ertapenem; GM, geometric mean; ke, elimination rate constant; Tmax, time to maximum concentration; Tmin, time to minimum concentration; Vd, volume of distribution; WCK 6777, ertapenem/zidebactam; τ, dosing interval; ss, steady state.