TABLE 4.
Summary of pharmacokinetics of nacubactam in the MAD studyd
| Parameterc | Part 1a |
Part 2a,b | Part 3 |
||
|---|---|---|---|---|---|
| Nacubactam, 1,000 mg (n = 6) | Nacubactam, 2,000 mg (n = 6) | Nacubactam, 4,000 mg (n = 6) | Single dose (day 1 or 2) nacubactam, 2,000 mg | Single dose (day 3) nacubactam, 2,000 mg, plus meropenem, 2,000 mg | |
| Cmax (μg/ml) | 36.6 (21) | 89.6 (15) | 179 (17) | 66.0 (14) | 65.0 (30) |
| tmax (h) | 1.00 (1.00 to 1.67) | 1.33 (0.90 to 1.67) | 1.50 (1.00 to 1.53) | 1.00 (1.00 to 1.67) | 1.00 (1.00 to 1.67) |
| AUC0–8h (μg·h/ml) | 118 (23) | 279 (13) | 496 (18) | 201 (15) | 204 (27) |
| AUC0–inf (μg·h/ml) | NA | NA | NA | 225 (18) | 224 (30) |
| t1/2 (h) | 2.66 (5) | 2.66 (5) | 2.69 (5) | 2.63 (30) | 2.38 (14) |
| CL (liters/h) | 8.50 (23) | 7.16 (13) | 8.06 (18) | 8.87 (18) | 8.93 (30) |
| CLR (liters/h) | 6.69 (27) | 6.23 (19) | 6.77 (19) | 8.52 (18) | 8.10 (32) |
| Vss (liters) | 21.9 (17) | 16.5 (13) | 20.1 (23) | 26.2 (33) | 25.8 (30) |
| Fe%0–8h | 81.9 (1) | 87.0 (11) | 83.9 (9) | 85.5 (13) | 82.7 (12) |
| Fe%0–24h | NA | NA | NA | 91.1 (10) | 88.4 (11) |
| Rac (Cmax) | 1.04 (8) | 1.08 (18) | 1.02 (18) | NR | NR |
| Rac (AUC0–8h) | 1.107 (8) | 1.06 (10) | 1.02 (7) | NR | NR |
q8h administration for 7 days. Data are from day 7 (part 1) or day 9 (part 2).
Cohort 4 excluded was from the table due to being single-dose administration only.
AUC0–inf, area under the plasma concentration-time curve from time zero to infinity; AUC0–8h, area under the plasma concentration-time curve from time zero to 8 h; CL, clearance; CLR, renal clearance; Cmax, maximum observed plasma concentration; Fe%0–8h, cumulative percentage of dose excreted in urine from time zero to 8 h; Fe%0–24h, cumulative percentage of dose excreted in urine from time zero to 24 h; MAD, multiple ascending dose; Rac (Cmax), accumulation ratio based on Cmax; Rac (AUC0–8h), accumulation ratio based on AUC0–8h; t1/2, apparent terminal elimination half-life; tmax, time to reach maximum plasma concentration; Vss, volume of distribution at steady state.
Data presented as geometric means and percent coefficient of variation, except tmax, which is given as medians (ranges). NA, not applicable; NR, not reported.