TABLE 7.
Summary statistics for free ZID 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 |
|---|---|---|---|---|---|
| Free zidebactam single-dose plasma PK parameters | |||||
| Cmax (µg/mL) | 64.35 (20) | 105.42 (16) | 98.41 (55) | 108.79 (11) | 124.99 (10) |
| Cmin (µg/mL) | 0.09 (22) | 0.07 (36) | 0.10 (39) | 0.14 (26) | 0.14 (34) |
| Tmax (h) | 0.50 (0.50–0.50) | 1.03 (1.02–1.03) | 1.00 (1.00–2.00) | 2.02 (1.03–2.02) | 2.03 (2.02–2.03) |
| Tmin (h) | 23.60 (18.00–23.70) | 23.60 (23.60–23.70) | 23.60 (18.00–23.60) | 23.60 (23.60–23.60) | 23.60 (23.60–23.70) |
| AUC(0–t) (µg h/mL) | 125.17 (8) | 257.74 (15) | 247.40 (42) | 379.75 (11) | 427.31 (16) |
| AUC(0–inf) (µg h/mL) | 126.50 (8) | 259.27 (15) | 249.11 (41) | 381.44 (11) | 429.33 (16) |
| AUC(0–24) (µg h/mL) | 126.34 (8) | 259.11 (15) | 248.60 (42) | 380.91 (11) | 428.67 (16) |
| AUC(0–last) (µg h/mL) | 126.34 (8) | 259.11 (15) | 248.60 (42) | 380.91 (11) | 428.67 (16) |
| t1/2 (h) | 2.75 (18) | 2.81 (14) | 2.63 (15) | 2.69 (9) | 2.71 (5) |
| CLT (L/h) | 7.91 (8) | 7.71 (15) | 8.03 (41) | 7.86 (11) | 6.99 (16) |
| ke (1/h) | 0.25 (18) | 0.25 (14) | 0.26 (14) | 0.26 (9) | 0.26 (5) |
| Vd (L) | 31.37 (12) | 31.18 (23) | 30.42 (40) | 30.52 (9) | 27.28 (17) |
| Free zidebactam multiple-dose plasma PK parameters | |||||
| Cmax,ss (µg/mL) | 57.89 (23) | 103.12 (18) | 83.36 (57) | 111.59 (7) | 111.81 (16) |
| Cmax,ss/dose ([µg/mL]/mg) | 0.06 (23) | 0.05 (18) | 0.04 (56) | 0.04 (7) | 0.04 (15) |
| Cmin,ss (µg/mL) | 0.12 (66) | 0.10 (38) | 0.17 (864) | 0.14 (23) | 0.11 (34) |
| Cavg,ss (µg/mL) | 5.03 (8) | 10.48 (20) | 9.77 (30) | 16.32 (8) | 15.83 (14) |
| Ct,ss (µg/mL) | 0.06 (169) | 0.07 (90) | 0.11 (2,318) | 0.14 (23) | 0.11 (34) |
| Tmax,ss (h) | 0.52 (0.25–0.60) | 1.00 (1.00–1.00) | 1.02 (1.00–2.00) | 2.02 (2.02–2.07) | 2.07 (2.02–2.23) |
| Tmin (h) | 24.00 (18.00–24.00) | 24.00 (18.10–24.00) | 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) | 120.70 (8) | 251.56 (20) | 234.14 (30) | 392.09 (8) | 380.11 (14) |
| AUC(0–τ),ss (µg h/mL) | 120.70 (8) | 251.56 (20) | 234.14 (30) | 392.09 (8) | 380.11 (14) |
| AUC(0–τ),ss/dose ([µg h/mL]/mg) | 0.12 (8) | 0.13 (20) | 0.12 (30) | 0.13 (8) | 0.13 (14) |
| t1/2 (h) | 2.55 (11) | 2.78 (15) | 3.13 (55) | 2.65 (7) | 2.70 (8) |
| CLT (L/h) | 8.28 (8) | 7.96 (20) | 8.54 (30) | 7.65 (8) | 7.89 (14) |
| Vd,ss (L) | 21.86 (10) | 18.79 (14) | 30.21 (197) | 20.17 (6) | 19.69 (13) |
| Linearity indexa | 0.95 (5) | 0.97 (13) | 0.94 (26) | 1.03 (7) | 0.89 (13) |
| RAUCb | 0.96 (5) | 0.97 (13) | 0.94 (26) | 1.03 (7) | 0.89 (13) |
| RCmaxc | 0.90 (15) | 0.98 (11) | 0.85 (40) | 1.03 (10) | 0.89 (13) |
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.