TABLE 5.
Summary statistics for free 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 |
|---|---|---|---|---|---|
| Free ertapenem single-dose plasma PK parameters | |||||
| Cmax (µg/mL) | 16.60 (17) | 34.00 (17) | 42.10 (22) | 58.45 (17) | 59.42 (19) |
| Cmin (µg/mL) | 0.10 (40) | 0.16 (42) | 0.14 (67) | 0.36 (24) | 0.28 (35) |
| Tmax (h) | 0.50 (0.50–0.50) | 1.00 (1.00–1.07) | 1.00 (1.00–1.00) | 2.02 (2.02–2.03) | 2.03 (2.02–2.03) |
| Tmin (h) | 23.60 (18.00–23.60) | 23.60 (18.00–23.70) | 23.60 (23.60–23.60) | 23.60 (23.40–23.60) | 23.60 (23.60–23.70) |
| AUC(0–t) (µg h/mL) | 39.92 (7) | 83.95 (19) | 102.81 (24) | 187.42 (15) | 190.43 (14) |
| AUC(0–inf) (µg h/mL) | 41.65 (7) | 85.93 (19) | 104.94 (24) | 190.81 (15) | 193.61 (14) |
| AUC(0–24) (µg h/mL) | 41.19 (7) | 85.25 (19) | 103.96 (23) | 188.86 (15) | 192.13 (14) |
| AUC(0–last) (µg h/mL) | 41.04 (7) | 85.03 (19) | 103.94 (23) | 188.66 (15) | 191.81 (14) |
| t1/2 (h) | 4.09 (11) | 3.83 (21) | 3.86 (15) | 3.96 (12) | 3.87 (10) |
| CLT (L/h) | 23.99 (7) | 23.28 (19) | 19.06 (24) | 15.70 (15) | 15.50 (14) |
| ke (1/h) | 0.17 (11) | 0.18 (21) | 0.18 (15) | 0.18 (12) | 0.18 (10) |
| Vd (L) | 141.43 (11) | 128.25 (12) | 106.20 (23) | 89.98 (20) | 86.55 (16) |
| Free ertapenem multiple-dose plasma PK parameters | |||||
| Cmax,ss (µg/mL) | 15.41 (24) | 38.18 (13) | 36.09 (23) | 57.65 (28) | 50.36 (28) |
| Cmax,ss/dose ([µg/mL]/mg) | 0.02 (24) | 0.02 (13) | 0.02 (23) | 0.02 (28) | 0.02 (28) |
| Cmin,ss (µg/mL) | 0.10 (28) | 0.12 (35) | 0.12 (60) | 0.23 (31) | 0.15 (59) |
| Cavg,ss (µg/mL) | 1.64 (6) | 3.51 (18) | 3.77 (16) | 7.01 (23) | 6.29 (19) |
| Cτ,ss (µg/mL) | 0.06 (53) | 0.07 (128) | 0.07 (88) | 0.23 (31) | 0.15 (58) |
| Tmax,ss (h) | 0.52 (0.25–0.60) | 1.00 (1.00–1.00) | 1.02 (0.50–1.02) | 2.02 (2.02–2.02) | 2.07 (2.02–2.23) |
| Tmin (h) | 24.00 (18.00–24.00) | 24.00 (18.00–24.10) | 24.00 (18.00–24.00) | 24.00 (24.00–24.00) | 24.00 (24.00–24.10) |
| AUC(0–24),ss (µg h/mL) | 39.48 (6) | 84.22 (18) | 90.51 (16) | 168.05 (23) | 150.93 (19) |
| AUC(0–τ),ss (µg h/mL) | 39.48 (6) | 84.22 (18) | 90.51 (16) | 168.05 (23) | 150.93 (19) |
| AUC(0–τ),ss/dose ([µg h/mL]/mg) | 0.04 (6) | 0.04 (18) | 0.05 (16) | 0.06 (23) | 0.05 (19) |
| t1/2 (h) | 3.89 (19) | 3.45 (19) | 3.38 (19) | 3.77 (10) | 3.76 (17) |
| CLT (L/h) | 25.35 (6) | 23.75 (18) | 22.09 (16) | 17.83 (23) | 19.86 (19) |
| Vd,ss (L) | 105.98 (14) | 72.51 (16) | 69.65 (13) | 56.84 (30) | 61.59 (29) |
| Linearity indexa | 0.95 (4) | 0.98 (4) | 0.86 (18) | 0.88 (9) | 0.78 (17) |
| RAUCb | 0.96 (4) | 0.99 (3) | 0.87 (18) | 0.89 (9) | 0.79 (17) |
| RCmaxc | 0.93 (11) | 1.12 (7) | 0.86 (37) | 0.99 (12) | 0.85 (28) |
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.