TABLE 2

Pharmacokinetic parameters of meropenem and/or vaborbactam following single or multiple dosesb

Cohort/dosea and treatmentnCmax (μg/ml)t1/2 (h)AUC0–inf (μg · h/ml), single doseAUC0–t (μg · h/ml), multiple doseVss (liters)CLT (liter/h)
Single doseMultiple doseSingle doseMultiple doseSingle doseMultiple doseSingle doseMultiple dose
Meropenem PK
    1/1,000:250
        Meropenem alone3216.9 (44.7)16.5 (58.0)1.0 (42.8)1.0 (55.5)51.6 (43.3)49.3 (55.7)24.9 (52.7)25.7 (77.3)19.4 (43.3)20.3 (55.6)
        Combination1618.6 (32.4)15.7 (34.5)1.0 (28.8)1.0 (33.4)56.1 (30.5)47.1 (32.5)25.2 (49.5)29.4 (62.8)17.8 (30.5)21.2 (32.8)
    2/1,000:1,000
        Meropenem alone1318.6 (47.4)16.4 (38.4)1.0 (35.3)0.9 (20.3)58.1 (47.7)49.9 (39.3)23.2 (49.1)23.2 (34.4)17.2 (47.7)20.1 (39.2)
        Combination1019.9 (46.6)17.0 (32.1)1.1 (45.2)0.9 (24.0)64.1 (51.0)53.9 (36.5)20.8 (50.7)23.1 (44.2)15.6 (51.0)18.5 (36.2)
    3/1,000:1,500
        Meropenem alone1920.9 (34.8)23.3 (59.1)0.89 (31.5)0.87 (33.2)64.6 (38.2)67. (55.9)18.9 (40.1)17.2 (51.5)15.5 (38.2)14.9 (55.9)
        Combination1420.9 (34.8)23.3 (59.1)0.89 (31.5)0.87 (33.2)64.6 (38.2)67. (55.9)21.3 (47.8)18.5 (52.7)15.6 (48.4)15.5 (48.0)
    4/1,000:2,000
        Meropenem alone1917.3 (37.4)15.9 (43.9)1.0 (47.5)1.0 (52.6)53.7 (43.0)50.7 (32.7)25.0 (47.0)25.2 (42.4)18.6 (43.0)19.7 (32.7)
        Combination1417.5 (23.7)15.8 (29.2)0.9 (45.5)1.1 (39.8)55.0 (27.0)47.9 (20.7)23.8 (29.7)25.5 (31.8)18.2 (27.0)20.9 (20.7)
    5/2,000:2,000
        Meropenem alone2040.9 (53.6)46.0 (59.6)1.1 (54.901.0 (46.0)125.7 (48.9)133.7 (56.4)22.2 (52.8)20.2 (47.9)15.9 (48.9)15.0 (56.4)
        Combination1645.7 (35.7)42.5 (48.5)1.3 (82.6)1.2 (56.5)139.3 (45.8)135.7 (46.8)21.7 (38.2)21.0 (42.5)14.4 (45.8)14.9 (45.8)
Vaborbactam PK
    1/1,000:250
        Vaborbactam alone405.2 (41.8)4.9 (37.0)1.1 (57.2)1.1 (50.3)17.2 (42.7)16.2 (46.8)22.2 (48.6)23.2 (46.0)14.5 (42.7)15.3 (45.9)
        Combination165.3 (40.2)4.6 (39.5)1.1 (52.0)1.2 (38.6)17.0 (38.3)14.6 (39.8)24.3 (49.8)27.0 (66.1)14.7 (38.3)16.9 (39.4)
    2/1,000:1,000
        Vaborbactam alone521.7 (42.3)1.5 (69.6)75.4 (48.0)21.9 (59.0)13.3 (48.0)
        Combination1023.3 (46.1)19.9 (29.7)1.5 (49.8)1.3 (61.8)79.4 (46.2)68.4 (39.0)20.2 (41.8)22.5 (29.3)12.6 (46.2)14.8 (37.4)
    3/1,000:1,500
        Vaborbactam alone736.3 (41.0)1.2 (49.3)117.8 (36.6)21.1 (68.4)12.7 (36.6)
        Combination1436.9 (37.0)32.6 (32.5)1.3 (44.7)1.4 (61.2)124.2 (40.4)114.7 (38.4)19.9 (38.2)19.4 (36.7)12.1 (40.4)13.3 (37.3)
    4/1,000:2,000
        Vaborbactam alone738.0 (28.8)1.3 (54.8)125.8 (35.1)22.8 (28.3)15.9 (35.0)
        Combination1440.0 (22.7)34.7 (34.6)1.4 (46.7)1.5 (56.3)132.8 (29.2)113.2 (29.8)23.8 (26.3)26.8 (35.0)15.1 (29.2)17.9 (28.7)
    5/2,000:2,000
        Vaborbactam alone849.5 (57.4)1.4 (37.7)151.9 (54.5)21.8 (43.5)13.2 (54.5)
        Combination1650.1 (42.6)54.7 (47.1)1.9 (61.9)1.6 (50.5)165.3 (45.2)192.6 (45.0)22.0 (41.0)19.3 (36.8)12.1 (45.2)10.7 (43.1)
  • a Doses are expressed as meropenem (mg):vaborbactam (mg).

  • b Values shown are geometric means (geometric coefficient of variation); AUC0–t, area under the plasma concentration-time curve from time zero to the last measurable concentration; AUCinf, area under the plasma concentration-time curve from time zero to infinity; CLT, total clearance; Cmax, maximum drug concentration in serum; fe, fraction of administered dose excreted over the urine collection interval, expressed as a percent; t1/2, terminal half-life over the sampling period; Vss, steady-state volume of distribution.