TABLE 2

Geometric mean (% coefficient of variation) PK parameters for durlobactam

PK parameterdNormal renal function (n = 8)RIESRD period
Mild (n = 6)Moderate (n = 6)Severe (n = 7)1 (n = 5)2 (n = 6)
Dose (mg)1,0001,0001,000500500500
Cmax (μg/ml)27.0 (19.3)33.3 (18.9)38.7 (20.9)25.5 (21.4)28.6 (27.5)21.9 (22.7)
Tmax (h)a3.0 (2.0–3.1)3.0 (2.0–3.0)3.0 (2.0–3.2)3.0 (3.0–4.0)3.0 (2.0–3.5)3.0 (3.0–4.0)
Half-life (h)2.3 (4.3)b3.0 (14.8)3.8 (21.9)5.4 (20.5)7.1 (36.6)7.1 (32.7)c
AUC0–last (h · μg/ml)109 (16.7)151 (19.1)209 (33.2)202 (24.0)278 (45.2)123 (28.5)
AUC0–inf (h · μg/ml)110 (17.6)b151 (19.1)209 (33.2)202 (24.0)280 (45.6)123 (32.1)c
CL (ml/h)9,090 (17.6)b6,640 (19.1)4,790 (33.2)2,470 (24.2)1,780 (45.6)4,070 (32.1)c
Vz (ml)30,600 (15.3)b28,500 (20.1)26,000 (12.6)19,200 (12.3)18,300 (13.0)41,900 (21.9)c
CLR or CLD (ml/h)6,080 (22.0)5,040 (20.8)3,420 (35.6)947 (53.8)7,600 (24.2)
Feu/FeHD0.66 (18.3)0.78 (7.1)0.72 (14.8)0.38 (29.1)0.33 (35.6)
  • a Median (range).

  • b n = 7.

  • c n = 5.

  • d AUC0–last or AUC0–inf, area under the concentration-time curve, time 0 to last or time 0 to infinity; CL, clearance; CLD, estimated hemodialysis recovery clearance; CLR, renal clearance; Cmax, peak plasma concentration; FeHD, fraction of dose removed by hemodialysis; Feu, fraction of the dose renally eliminated; Tmax, time to peak plasma concentration; Vz, terminal volume of distribution.