TABLE 2.
Single-dose daptomycin PK parametersa
| Patient population | Wt (kg) | Dose (mg/kg) | Cmax (μg/ml) | C24 (μg/ml) | AUC0-∞ (μg·h/ml) | t1/2 (h) | CL | VSS | V1 (ml) | Vz | MRT (h) | Ae (% of dose) | CLR (ml/h/kg) | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Healthy, male volunteers (n = 6) | 78.5 ± 9.0 | 4 | 77.5 ± 8.3 | 529.7 ± 13 | 7.74 ± 0.63 | 9.84 ± 0.26 ml/min | 6,057 ± 679 ml | 3,420 ± 1,070 | 6,350 ± 533.4 ml | 10.94 ± 0.93 | 59.7 ± 10.2 | Wise et al. (31) | ||
| Young, healthy volunteers ages 18-30 yr (n = 11) | 64.9 ± 9.76 | 4 | 42.32 (15.35) | <LLQ | 300.64 (11.53)b | 6.79 (7.78) | 15.09 (16.35) ml/h/kg | 0.14 (12.86) liter/kg | 0.15 (12.81) liter/kg | 9.05 (6.00) | 42.29 (16.42) | 7.20 (25.53) | Dvorchik et al. (12) | |
| Old, healthy volunteers ages ≥75 yr (n = 12) | 77.0 ± 8.16 | 4 | 43.98 (16.67) | 6.38 (29.43) | 473.66 (23.21)b | 11.85 (18.98) | 9.86 (25.09) ml/h/kg | 0.15 (28.83) liter/kg | 0.17 (28.93) liter/kg | 15.91 (17.25) | 34.31 (45.85) | 4.27 (29.97) | Dvorchik et al. (12) | |
| Moderately obese adult volunteers (n = 6) | 85.7 ± 9.0 | 4 | 57.75 (12.59) | 3.44 (52.34) | 420.53 (15.99)c | 7.34 (12.67) | 16.24 (5.17)c ml/h/kg | 0.15 (11.27) liter/kg | 51.82 (12.44) | 9.35 (13.71) | Dvorchik and Damphousse (14) | |||
| Nonobese adult volunteers (n = 6) | 64.3 ± 7.0 | 4 | 46.28 (14.51) | <LLQ | 322.37 (10.29)c | 6.83 (9.67) | 14.72 (6.63)c ml/h/kg | 0.13 (5.78) liter/kg | 52.33 (15.63) | 8.37 (12.71) | Dvorchik and Damphousse (14) | |||
| Morbidly obese adult volunteers (n = 6) | 125.8 ± 17.0 | 4 | 67.00 (10.37)c | 5.88 (49.36) | 547.78 (24.61)c | 8.12 (21.08) | 7.82 (19.78)c ml/h/kg | 0.18 (14.55)c liter/kg | 42.74 (13.68) | 8.06 (31.26) | Dvorchik and Damphousse (14) | |||
| Nonobese adult volunteers (matched controls) (n = 6) | 4 | 53.22 (11.31)c | 3.39 (90.43) | 418.76 (24.91)c | 8.04 (29.05) | 10.19 (32.53)c ml/h/kg | 0.11 (16.48)c liter/kg | 48.64 (17.29) | 5.88 (18.71) | Dvorchik and Damphousse (14) | ||||
| Morbidly obese adult volunteers (n = 7) | 114.3 ± 15.8 | 4 | 67.3 ± 12.3c | 6.55 ± 2.31c | 581 ± 104c | 8.68 ± 1.67 | 0.0071 ± 0.0013c liter/h/kg | 0.09 ± 0.01c liter/kg | Pai et al. (22) | |||||
| Nonobese adult volunteers (matched controls) (n = 7) | 58.8 ± 6.2 | 4 | 42.3 ± 11.9c | 3.39 ± 0.79c | 346 ± 63c | 7.72 ± 0.76 | 0.012 ± 0.0020c liter/h/kg | 0.13 ± 0.02c liter/kg | Pai et al. (22) | |||||
| Adult volunteers w/hepatic impairment (n = 10) | 92.66 | 6 | 113.72 (14.68) | 867.43 (22.75) | 8.97 (19.28) | 7.10 (19.54) ml/h/kg | 0.08 (15.12) liter/kg | 12.04 (20.02) | 49.27 (39.19) | 3.65 (49.28) | Dvorchik et al. (12) | |||
| Adult volunteers (matched controls) (n = 9) | 84.18 | 6 | 118.33 (12.81) | 928.02 (12.91) | 9.44 (8.77) | 6.55 (12.85) ml/h/kg | 0.08 (13.22) liter/kg | 12.44 (9.55) | 39.81 (21.59) | 2.72 (17.70) | Dvorchik et al. (12) | |||
| Healthy, adult men (n = 6) | 15% of IBW | 6 | 82 ± 20.4 | 598 ± 110 | 8.06 | 10.26 ± 1.68 ml/h/kg | 0.12 ± 0.020 liter/kgd | 3.84 ± 1.08 | Woodworth et al. (32) |
a
Data are presented as means ± SDs or mean (percent CV). Ae, amount excreted unchanged; CLR, renal clearance; LLQ, lower limit of quantitation (which was 3.3 μg/ml); IBW, ideal body weight. The other abbreviations are defined in the text.
b
P ≤ 0.0001
c
P < 0.05.
d
The data represent V in the elimination phase.