TABLE 6.
Summary statistics for total zidebactam single- and multiple-dose PK parameters in plasma by treatment groupd,e
| PK parameter (units) | WCK 6777 2 g | ZID 2 g | WCK 6777 4 g | ZID 3 g | WCK 6777 6 g |
|---|---|---|---|---|---|
| Total zidebactam single-dose plasma PK parameters | |||||
| Cmax (µg/mL) | 69.67 (15) | 120.41 (22) | 133.51 (16) | 111.71 (10) | 128.42 (11) |
| Cmin (µg/mL) | 0.09 (37) | 0.11 (72) | 0.10 (44) | 0.13 (28) | 0.15 (30) |
| Tmax (h) | 0.50 (0.50–0.50) | 1.03 (1.02–1.03) | 1.00 (1.00–1.00) | 2.02 (1.03–2.02) | 2.03 (2.02–2.03) |
| Tmin (h) | 18.00 (18.00–23.60) | 23.60 (18.00–23.70) | 23.60 (18.00–23.60) | 23.60 (23.60–23.60) | 23.60 (23.60–23.70) |
| AUC(0–t) (µg h/mL) | 140.00 (8) | 302.40 (18) | 320.50 (20) | 379.92 (9) | 442.32 (14) |
| AUC(0–inf) (µg h/mL) | 141.33 (8) | 303.92 (18) | 322.04 (20) | 381.76 (9) | 444.34 (14) |
| AUC(0–24) (µg h/mL) | 141.17 (8) | 303.60 (18) | 321.76 (20) | 381.59 (9) | 443.70 (14) |
| AUC(0–last) (µg h/mL) | 141.17 (8) | 303.42 (18) | 321.35 (20) | 381.44 (9) | 443.70 (14) |
| t1/2 (h) | 2.35 (15) | 2.60 (14) | 2.57 (12) | 2.61 (9) | 2.71 (6) |
| CLT (L/h) | 7.07 (8) | 6.58 (18) | 6.21 (20) | 7.86 (9) | 6.75 (14) |
| ke (1/h) | 0.30 (15) | 0.27 (14) | 0.27 (12) | 0.27 (9) | 0.26 (6) |
| Vd (L) | 23.97 (14) | 24.67 (28) | 23.05 (22) | 29.56 (10) | 26.43 (16) |
| Total zidebactam multiple-dose plasma PK parameters | |||||
| Cmax,ss (µg/mL) | 63.87 (17) | 115.71 (16) | 130.69 (18) | 109.41 (7) | 113.79 (16) |
| Cmax,ss/dose ([µg/mL]/mg) | 0.06 (17) | 0.06 (16) | 0.07 (18) | 0.04 (7) | 0.04 (16) |
| Cmin,ss (µg/mL) | 0.13 (49) | 0.12 (68) | 0.10 (46) | 0.13 (27) | 0.12 (36) |
| Cavg,ss (µg/mL) | 5.56 (8) | 11.94 (20) | 12.83 (19) | 16.05 (7) | 16.52 (14) |
| Cτ,ss (µg/mL) | 0.02 (68) | 0.06 (89) | 0.05 (176) | 0.13 (28) | 0.12 (35) |
| Tmax,ss (h) | 0.52 (0.25–0.60) | 1.00 (1.00–1.00) | 1.02 (1.00–1.02) | 2.02 (2.02–2.07) | 2.07 (2.02–2.23) |
| Tmin (h) | 18.00 (18.00–24.00) | 24.00 (18.00–24.00) | 24.00 (18.00–24.00) | 24.00 (24.00–24.10) | 24.00 (24.00–24.10) |
| AUC(0–24),ss (µg h/mL) | 133.35 (8) | 286.34 (20) | 308.35 (19) | 384.53 (7) | 396.60 (14) |
| AUC(0–τ),ss (µg h/mL) | 133.35 (8) | 286.34 (20) | 308.35 (19) | 384.53 (7) | 396.60 (14) |
| AUC(0–τ),ss/dose ([µg h/mL]/mg) | 0.13 (8) | 0.14 (20) | 0.15 (19) | 0.13 (7) | 0.13 (14) |
| t1/2 (h) | 2.32 (15) | 2.64 (12) | 2.47 (24) | 2.69 (3) | 2.65 (10) |
| CLT (L/h) | 7.50 (8) | 6.98 (20) | 6.49 (19) | 7.80 (7) | 7.56 (14) |
| Vd,ss (L) | 18.04 (14) | 16.57 (18) | 13.88 (21) | 20.33 (7) | 19.35 (13) |
| Linearity indexa | 0.94 (4) | 0.94 (13) | 0.96 (5) | 1.01 (8) | 0.89 (11) |
| RAUCb | 0.94 (4) | 0.94 (13) | 0.96 (5) | 1.01 (8) | 0.89 (11) |
| RCmaxc | 0.92 (15) | 0.96 (11) | 0.98 (12) | 0.98 (13) | 0.89 (17) |
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; 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; ZID, zidebactam; τ, dosing interval; ss, steady state.