TABLE 3.
Mean omadacycline pharmacokinetics (PK) in plasma and urine (PK population)
| Parameter | Results by group on daya: |
|||||
|---|---|---|---|---|---|---|
| 1 |
5 |
|||||
| Group 1 (i.v. 200 mg → p.o. 300 mg [n = 11]) |
Group 2 (p.o. 300 mg [n = 10]) |
Group 3 (p.o. 450 mg [n = 10]) |
Group 1b (i.v. 200 mg → p.o. 300 mg [n = 10]) |
Group 2 (p.o. 300 mg [n = 10]) |
Group 3 (p.o. 450 mg [n = 10]) |
|
| Plasmac | ||||||
| Cmax (μg/ml) | 2.16 (59.0) | 0.88 (25.6) | 0.99 (30.6) | 1.12 (58.8) | 1.12 (37.2) | 1.49 (36.2) |
| Tmax (h) | 0.75 (0.72, 1.60) | 3.0 (2.0, 4.0) | 3.0 (0.97, 4.0) | 3.0 (0.0, 4.0) | 3.0 (2.0, 8.0) | 3.0 (0.50, 8.0) |
| AUC0–24 (μg · h/ml) | 16.02 (28.7) | ND | ND | 13.16 (59.7) | 13.50 (33.7) | 19.83 (30.8) |
| AUC0–12 (μg · h/ml) | ND | 6.26 (18.9) | 6.85 (23.2) | ND | ND | ND |
| T1/2 (h) | 11.38 (13.6) | ND | ND | ND | ND | ND |
| Clearance (liters/h) | 10.27 (15.1) | ND | ND | ND | ND | ND |
| V (liters) | 167.57 (17.6) | ND | ND | ND | ND | ND |
| Cmin (μg/ml) | ND | ND | ND | 0.29 (60.4) | 0.32 (35.4) | 0.48 (27.6) |
| Urined | ||||||
| Ae0–24 (mg)e | 40.70 (44) | 39.24 (34) | 35.95 (33) | 32.27 (79) | 38.21 (52) | 54.87 (67) |
| Total dose within 24 h (mg) (delivery method) | 200 (i.v.) | 600 (p.o.) | 900 (p.o.) | 300 (p.o.) | 300 (p.o.) | 450 (p.o.) |
| fe0–24 (%) (dose administered) | 20.4 | 6.5 | 4.0 | 10.8 | 12.7 | 12.2 |
| Concentration (μg/ml) at timef | ||||||
| 0–4 h | 65.36 (53.02) | 14.00 (9.69) | 23.01 (29.94) | 42.71 (43.37) | 30.90 (18.90) | 35.99 (24.12) |
| 4–8 h | 43.55 (31.52) | 19.09 (9.47) | 20.54 (19.19) | 26.09 (18.06) | 29.11 (21.37) | 48.12 (46.01) |
| 8–12 h | 32.41 (20.32) | 19.98 (19.23) | 11.70 (6.82) | 33.24 (34.55) | 25.35 (16.99) | 30.47 (25.84) |
| 12–24 h | 22.41 (17.75) | 20.77 (11.92) | 25.71 (16.24) | 21.48 (21.97) | 17.94 (12.00) | 30.28 (23.57) |
| CLRg (liters/h)f | 2.64 (1.21) | ND | ND | 2.42 (0.92) | 2.71 (1.01) | 2.80 (2.29) |
Omadacycline doses are given in parentheses after each group. i.v., intravenous; p.o., oral; ND, not determined.
One patient in group 1 withdrew consent on study day 2 and did not complete the day 5 PK assessment.
Arithmetic mean (percent coefficient of variation [%CV]) is shown for all parameters except Tmax, which is shown as median and range (minimum, maximum). Cmax, mean maximum (peak) observed plasma concentration; Tmax, median time to maximum (peak) observed plasma concentration; AUC0–24, area under concentration-time curve from 0 to 24 h.; AUC0–12, area under the concentration-time curve from 0 to 12 h; T1/2, half-life; V, volume of distribution; Cmin, mean minimum observed plasma concentration.
Ae0–24, amount excreted unchanged in urine from 0 to 24 h; fe0–24, fraction of dose excreted in urine from 0 to 24 h.
Data shown are mean (%CV).
Data shown are mean (standard deviation [SD]).
CLR, renal clearance.