Table 1.
Pharmacokinetic Exposure Parameters (Geometric Mean, %CV) for Plasma, Lung, and ELF after a Single Dose or a Multiple Dose Series of Different Dose Levels (10, 50, 150, or 200 mg/kg) of Spectinamide-1599 given by IPA, SC, or IV Administration to Micea
| plasma |
lung |
ELF |
|||||
|---|---|---|---|---|---|---|---|
| dose (mg/kg) | Cmax (μg/mL) | AUClast (μg h/mL) | Cmax (μg/g) | AUClast (μg h/g) | Cmax (μg/mL) | AUClast (μg h/mL) | |
| single dose | |||||||
| IPA | 10 | 5.92 (66) | 5.51 (11) | 83.1 (15) | 162 (7.7) | 627 (44) | 747 (14) |
| IPA | 50 | 36.4 (35) | 23.2 (23) | 168 (49) | 332 (11) | 2137 (69) | 1830 (46) |
| IPA | 150 | 128 (125) | 59.5 (27) | 1620 (26) | 735 (13) | 1698 (99) | 1950 (26) |
| IV | 10 | 35.1 (16) | 7.52 (9.7) | 4.84 (25) | 3.79 (6.3) | 37.7 (13) | 41.0 (22) |
| SC | 50 | 88.5 (28) | 40.4 (13) | 18.6 (21) | 19.1 (7.5) | 113 (37) | 127 (21) |
| SCb | 200 | 191 (8.4) | 158 (6.1) | 8.82 (12) | 52.9 (23) | ND | ND |
| multiple doses: once daily (QD5) | |||||||
| IPA | 10 | 9.61 (52) | 3.56 (27) | 218 (21) | 227 (19) | 292 (144) | 307 (91) |
| IPA | 50 | 87.3 (69) | 39.8 (33) | 1043 (64) | 954 (20) | 2058 (81) | 812 (41) |
| IPA | 150 | 241 (92) | 96.9 (42) | 2409 (63) | 1910 (24) | 2537 (11) | 2100 (56) |
| IV | 10 | 31.0 (6.2) | 6.37 (5.8) | 3.97 (13) | 3.94 (16) | 61.1 (25) | 32.7 (48) |
| SC | 200 | 729 (13) | 471 (9.2) | 29.6 (3.8) | 69.1 (3.6) | 362 (23) | 297 (24) |
| multiple doses: once every other day (TIW) | |||||||
| IPA | 10 | 4.57 (54) | 5.35 (36) | 113 (41) | 150 (39) | 332 (51) | 307 (62) |
| IPA | 50 | 45.0 (44) | 24.3 (31) | 955 (72) | 789 (25) | 341 (86) | 237 (66) |
| IPA | 150 | 121 (78) | 61.7 (23) | 1330 (113) | 968 (39) | 3178 (69) | 1530 (22) |
| SC | 200 | 653 (11) | 424 (10) | 30.3 (29) | 72.0 (11) | 161 (48) | 401 (13) |
a
Cmax, maximum observed plasma concentration; AUClast, area under the concentration time curve until the last measured concentration. For multiple dose administrations, AUClast represents exposure after the last dose of the dosing series.
b
Previously reported in ref 10.