Table 6.
Amphotericin B: primary and secondary pharmacokinetic parameters based on non-compartmental analyses and individual-based compartmental models
| Study | Patients | Weight (kg) | Daily dose | Sampling day | C max (µg/mL) | V d (L/kg) | V ss (L/kg) | CL (mL/h/kg) | AUCa (µg·h/mL) | t ½ (h) |
|---|---|---|---|---|---|---|---|---|---|---|
| L-AMB | ||||||||||
| Gubbins et al. [86] | Peripheral stem cell transplant (PSCT) patients | 71.7 ± 13.3 | 1.0 mg/kg, 15 days | Day 1 Day 7 |
8.1 ± 4.2 13.5 ± 9.1 |
0.19 ± 0.14 0.16 ± 0.20 |
NA | 15.6 ± 10.8 10.6 ± 10.6 |
112.2 ± 75.3b
333.7 ± 548b |
9.7 ± 3.1 13.0 ± 11.8 |
| 83.9 ± 26.1 | 7.5 mg/kg weekly, 2 weeks | Day 1–7 Day 7–15 |
95.5 ± 39.9 52.3 ± 19.1 |
0.17 ± 0.20 0.47 ± 0.22 |
NA | 8.9 ± 11.0 21.6 ± 8.8 |
1887 ± 1344b
384.7 ± 126.3b |
19.2 ± 1.8 36.4 ± 24.4 |
||
| 87.5 ± 27.1 | 15 mg/kg, single dose | Day 1–8 | 206.3 ± 89.1 | 0.28 ± 0.22 | NA | 5.6 ± 4.4 | 5019 ± 4199b | 32.8 ± 12.2 | ||
| Walsh et al. [89] | Neutropenic patients | NA | 1.0 mg/kg, various durations | Day 1 Last day |
NA | 0.58 ± 0.40 0.16 ± 0.04 |
0.44 ± 0.27 0.14 ± 0.05 |
39 ± 22 17 ± 6 |
32 ± 15b
66 ± 21b |
10.7 ± 6.4 7.0 ± 2.1 |
| 2.5 mg/kg, various durations | Day 1 Last day |
NA | 0.69 ± 0.85 0.18 ± 0.13 |
0.40 ± 0.37 0.16 ± 0.09 |
51 ± 44 22 ± 15 |
71 ± 36b
213 ± 196b |
8.1 ± 2.3 6.3 ± 2.0 |
|||
| 5.0 mg/kg, various durations | Day 1 Last day |
NA | 0.22 ± 0.17 0.11 ± 0.08 |
0.16 ± 0.10 0.10 ± 0.07 |
21 ± 14 11 ± 6 |
294 ± 102b
621 ± 371b |
6.4 ± 2.1 6.8 ± 2.1 |
|||
| 7.5 mg/kg, various durations | Day 1 Last day |
NA | 0.26 ± 0.15 0.20 ± 0.07 |
0.18 ± 0.10 0.17 ± 0.05 |
25 ± 22 20 ± 7 |
534 ± 429b
417 ± 155b |
8.5 ± 3.9 6.9 ± 0.9 |
|||
| Walsh et al. [88] | Immunocompromised patients with invasive fungal infections | NA | 7.5 mg/kg, various durations | Day 1 Last 7 |
75.9 ± 58.4 115.1 ± 104.9 |
0.22 ± 0.18 0.14 ± 0.10 |
0.24 ± 0.18 0.14 ± 0.11 |
23 ± 14 15 ± 11 |
692 ± 834 1333 ± 2153 |
6.8 ± 1.9 6.0 ± 0.8 |
| 10.0 mg/kg. various durations | Day 1 Last 7 |
119.6 ± 69.8 164.7 ± 119.7 |
0.23 ± 0.24 0.16 ± 0.17 |
0.22 ± 0.23 0.14 ± 0.14 |
18 ± 19 12 ± 12 |
1062 ± 971 1919 ± 2056 |
8.0 ± 1.5 8.4 ± 2.6 |
|||
| 12.5 mg/kg. various durations | Day 1 Last 7 |
116.3 ± 47.8 147.4 ± 69.2 |
0.18 ± 0.13 0.16 ± 0.10 |
0.16 ± 0.07 0.13 ± 0.08 |
16 ± 6 13 ± 7 |
860 ± 390 1168 ± 991 |
7.1 ± 3.5 8.2 ± 2.5 |
|||
| 15.0 mg/kg. various durations | Day 1 Last 7 |
105.1 ± 30.9 178.6 ± 49.0 |
0.33 ± 0.12 0.18 ± 0.09 |
0.23 ± 0.09 0.14 ± 0.06 |
25 ± 8 14 ± 7 |
554 ± 30.9 1152 ± 617 |
9.0 ± 3.1 9.0 ± 0.9 |
|||
| L-AMB + D-AMB | ||||||||||
| Bekersky et al. [87] | Healthy volunteers | |||||||||
| L-AMB | 79 ± 11 | 2 mg/kg, single dose | Single dose | 22.9 ± 10 | 1.63 ± 0.88 | 0.774 ± 0.55 | 9.7 ± 5.4 | 171 ± 126 288 ± 209b |
t
½,α: 0.56 ± 0.48 t ½,β: 6.0 ± 2.1 t ½,γ: 152 ± 116 |
|
| D-AMB | 77 ± 9 | 0.6 mg/kg, single dose | Single dose | 1.43 ± 0.2 | 2.34 ± 0.20 | 1.81 ± 0.24 | 13.1 ± 2.0 | 13.9 ± 2.0 46.6 ± 7.2b |
t
½,α: 0.17 ± 0.14 t ½,β: 6.8 ± 1.6 t ½,γ: 127 ± 30 |
|
| Heinemann et al. [95] | Critically ill patients | |||||||||
| L-AMB | 72 (57–85) | 1.2–4.2 mg/kg | Steady state | 14.4 (6.4–89.0) | 0.42 (0.055–0.93) | NA | 0.363 (0.036–0.942) mL/min | 171 (53.1–1380) |
t
½,α: 1.65 (1.25–5.22) t ½,β: 13.1 (8.7–41.4) |
|
| D-AMB | 70 (50–120) | 1.0 mg/kg | Steady state | 1.70 (1.45–2.07) | 2.41 (1.12–4.32) | NA | 1.20 (0.59–1.91) mL/min | 18.65 (9.73–28.30) | t ½,β: 26.8 (9.9–37.0) | |
| D-AMB | ||||||||||
| Ayestarán et al. [133] | Neutropenic patients | 64.4 (mean) | 0.7–1 mg/kg | Day 1 | 2.83 ± 1.17 | NA | 0.56 ± 0.15 | 33.0 ± 14.3 | 29.0 ± 15.5 |
t
½,α: 0.64 ± 0.24 t ½,β: 15.2 ± 5.25 |
| Benson and Nahata [134] | Paediatric patients | 21.6 ± 13.3 | 0.25–1.5 mg/kg | Various | 1.64 (0.7–10.0) | 0.71 ± 0.23 | NA | 21.0 ± 1.8 | NA | 18.1 ± 6.6 |
| Kan et al. [135] | Healthy volunteers | 74.2 (55–87) | 0.1 mg/kg | Various | 0.551 ± 0.025 | NA | 0.50 ± 0.05 | 10 ± 1 | 3.9 ± 0.43 | 30.8 ± 4.1 |
| 0.25 mg/kg | Various | 0.984 ± 0.056 | NA | 0.74 ± 0.13 | 10 ± 1 | 8.7 ± 0.76 | 50.0 ± 11.3 | |||
| Koren et al. [102] | Infants/children | NA | 0.5–1 mg/kg | Various | NA | 0.378 | NA | 26 ± 5 | NA | 9.93 ± 1.5 |
Data given as either mean ± standard deviation or median (range)
Trough plasma concentration not included as it was only documented for Bekersky et al. [87]
AUC area under the concentration–time curve, CL clearance, C max peak plasma concentration, D-AMB amphotericin B deoxycholate, L-AMB liposomal amphotericin B, NA not available, t ½ plasma half-life, t ½,α distribution half-life, t ½,β elimination half-life, t½,γ terminal half-life, V d volume of distribution, V ss volume of distribution at steady state
aAUC from zero to 24 h after dose (AUC24), unless indicated otherwise
bAUC from zero to infinity (AUC∞)