TABLE 6

Excretion of TBPM-PI-HBr in urine and renal clearance for SAD and MAD phases

Phase, drug, and doseMean (% CV)
Fasted (day 1)Fed (day 7)
Fe, 0–4 hFe, 0–24 hCLR,d 0–24 h
(liters/h)
Fe, 0–4 hFe, 0–24 hCLR, 0–24 h
(liters/h)
SAD phase
    TBPM-PI-HBr
        12 h, 100 mg (n = 6)13.8 (40.2)21.4 (40.4)18.5 (21.0)
        12 h, 300 mg (n = 6)19.8 (34.9)28.5 (31.4)17.6 (20.9)17.0 (99.0)53.8 (14.1)19.0 (29.0)
        12 h, 600 mg (n = 9)14.4 (36.0)20.8 (28.6)18.9 (45.5)13.8a (97.0)62.7a (22.7)21.8a (28.6)
        12 h, 900 mg (n = 6)15.0 (34.2)24.6 (22.5)19.7 (22.0)
        2 h, 300 mg (n = 6)55.7 (16.1)59.1 (14.1)18.9 (11.9)13.2 (119.4)45.1 (39.8)19.9 (50.0)
        4 h, 300 mg (n = 6)35.8 (32.9)40.3 (19.3)15.2 (34.7)25.6 (80.7)50.9 (29.3)22.7 (38.5)
        4 h, 600 mg (n = 6)49.9 (27.3)54.9 (25.8)18.6 (14.4)31.3 (86.5)61.8 (30.9)20.1 (41.0)
        6 h, 300 mg (n = 6)29.1 (14.8)35.0 (13.7)19.0 (19.0)32.8 (34.8)58.0 (12.0)20.9 (21.7)
        IR, 100 mg (n = 6)58.4 (25.9)59.7 (25.7)17.0 (28.5)
        IR, 300 mg (n = 6)44.6 (23.4)47.1 (22.1)17.5 (19.1)34.9 (41.0)46.0 (18.5)17.5 (16.8)
        IR, 600 mg (n = 6)44.5 (22.0)47.8 (20.4)18.2 (22.7)37.6 (63.0)49.2 (37.5)16.4 (22.2)
        IR, 900 mg (n = 6)46.2 (47.0)53.5 (27.6)17.0 (18.5)
    Orapenem 300 mg (n = 8)58.3 (13.1)59.2 (13.2)12.8 (43.0)50.9b (20.8)55.1b (22.3)15.7b (33.4)
MAD phase
    Orapenem
        300 mg q8h (n = 6)56.0 (35.2)56.9 (34.6)16.7 (26.0)35.7 (76.5)39.4c (63.7)11.9c (56.8)
        600 mg q8h (n = 6)63.7 (9.6)65.6 (7.9)15.2 (20.3)27.4 (94.7)28.8 (88.4)7.5 (89.3)
  • a n = 6.

  • b n = 7.

  • c n = 4.

  • d CLR, renal clearance.