Article Figures & Data
Figures
- FIG. 1.
Mean tigecycline concentrations in serum in the single ascending dose study in fasting subjects as 1-h infusions (A), as 1-h infusions in the 200-mg dose group (B), and as 4-h infusions (C).
- FIG. 2.
Tigecycline concentrations (mean plus the standard deviation) serum in multiple ascending dose study on day 1 (A) and day 10 (B).
- FIG. 3.
Relationship between tigecycline dose in the single ascending dose study and Cmax (A) and AUC (B).
Tables
- TABLE 1.
Tigecycline regimen description
Study Cohort No. active/no. placebo Dosage regimen Infusion duration (h) Infusion vol (ml) Fasted or fed Antiemetic medication SAD 1 6/2 12.5 mg 1 250 Fasted None 2 6/2 25 mg 1 250 Fasted None 3 6/2 50 mg 1 250 Fasted None 4 6/2 75 mg 1 250 Fasted None 5 6/2 100 mg 1 250 Fasted None 6 6/2 200 mg 1 250 Fasted None 7 6/2 200 mg 4 250 Fasted None 8 6/2 200 mg 1 250 Fed None 9 6/2 300 mg 1 250 Fed None 10 6/2 300 mg 4 250 Fed None 11 6/2 200 mg 1 250 Fasted Ondansetron MAD 1 6/2 25 mg q12h 1 250 Fed None 2 6/2 50 mg q12h 1 250 Fed None 3 6/2 100 mg q12h 1 250 Fed None 4 6/2 75 mg q12h 1 250 Fed None VVIR 1 6/3 100 mg + 50 mg q12h 1 100 Fed None 2 7/3 100 mg + 50 mg q12h 0.5 100 Fed None 3 6/3 100 mg + 50 mg q12h 1 250 Fed None - TABLE 2.
Mean pharmacokinetic parameters (%CV) of tigecycline after various single i.v. doses in SAD study
Parameter Mean valuea (% CV) after: P 1-h infusion (group no., tigecycline [mg], fasting or fed) 4-h infusion (group no., tigecycline [mg], fasting or fed) 1, 12.5 fasting 2, 25, fasting 3, 50, fasting 4, 75, fasting 5, 100, fasting 6, 200, fasting 8, 200, fed 11, 200, fastingb 9, 300, fed 7, 200, fasting 10, 300, fed C max (ng/ml) 108.5 (10) 252 (25) 383 (17) 566 (14) 911 (29) 1,643 (18) 1,528 (22) 2,189 (30) 2,817 (17) 680 (22) 960 (10) 0.001 AUC (ng h/ml) 753 (68) 2,255 (45) 2,558 (21) 3,658 (27) 6,396 (10) 12,426 (23) 11,719 (19) 14,462 (17) 17,856 (10) 14,237 (22) 16,732 (16) 0.06 CL (l/h/kg) 0.29 (67) 0.20 (50) 0.28 (14) 0.29 (16) 0.20 (13) 0.25 (22) 0.22 (12) 0.20 (19) 0.25 (11) 0.24 (11) 0.26 (13) 0.27 V ss (l/kg) 2.8* (34) 6.4* (20) 6.4* (31) 7.5* (10) 8.6 (18) 11 (25) 13 (18) 12 (43) 12 (20) 14 (11) 12 (24) 0.001 t 1/2 (h) 11* (84) 32* (64) 18* (21) 21* (25) 38 (14) 42 (28) 54 (28) 53 (20) 46 (13) 58 (14) 42 (23) 0.001 CLR (l/h) ND ND ND ND 2.6 (26) 3 (50) 2.2 (22) 1.8 (24) 2.7 (23) NA 2 (28) 0.13 fe (%) 2.1 (113) 6.5 (39) 1.9 (72) 8 (37) 11 (25) 12 (31) 7.8 (25) 8.5 (38) 10.4 (22) NA 8 (39) 0.001 - TABLE 3.
Mean pharmacokinetic parameters of tigecycline after various i.v. doses infused over a 1-h period q12h in the MAD study
Tigecycline dose group (mg) Mean Value (%CV) at: Day 1 Day 10a Cmax (ng/ml) AUC0-τ (ng h/ml) Cmax (ng/ml) AUCss (ng h/ml) t1/2 (h) CL (l/h/kg) Vss (l/kg) 25 261 (14) 796 (8) 324 (17) 1,482 (18) 49.3 (72) 0.20 (17) 8.6 (23) 50 487 (17) 1,440 (14) 621 (15) 3,069 (12) 36.9 (32) 0.20 (9) 7.2 (7) 100 816 (15) 2,389 (13) 1,173 (15) 4,980 (19) 66.5 (34) 0.24 (20) 9.1 (32) ↵ a Day 10 values for the 100-mg tigecycline dose group are actually day 9 values.
- TABLE 4.
Trough concentrations of tigecycline among various dose groups after multiple doses of tigecycline given as a 1-h infusion in the MAD study
Day Mean (% cv) concn (ng/ml)a at: P 25 mg 50 mg 100 mg 7 86 (28) 153 (13) 214 (13) 0.07 8 81 (34) 195 (15) 255 (16) 0.12 9 83 (28) 204 (17) 257 (17) 0.06 10 87 (26) 145 (16) NA 0.23 ↵ a For comparison among dose groups, concentrations were dose normalized to the 100-mg dose before statistical analysis. For the 25-, 50-, and 100-mg dose groups, the P values were 0.98, 0.01, and 0.37, respectively. NA, not available.
