Table 7.
Amphotericin B: primary and secondary pharmacokinetic parameters derived from population-based compartmental studies
| Study | Patients | Weight (kg) | Daily dose | C max (µg/mL) | C trough (µg/mL) | V central (L) | CL (L/h) | V peripheral (L) | Q (L/h) | AUC (µg·h/mL) | t ½ (h) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Compartmental (population based) | |||||||||||
| Hong et al. [92] | Paediatric patients with malignant disease (L-AMB) | 28.8 (mean) | 0.8–5.9 mg/kg | NA | NA | 3.12 (40%)a
IOV: 56% |
0.44 (27%)a
IIV: 10% IOV: 46% |
18.0 (40%) IIV: 74% |
0.73 (18%) IIV: 77% |
NA | Terminal t ½: 59.4 ± 36.5 |
| Hope et al. [90] | Patients with suspected invasive fungal infection (L-AMB) |
68 (mean) | Intermittent: 10 mg/kg (day 1), 5 mg/kg (day 3/6) Conventional: 3 mg/kg, 14 days |
NA | NA | 20.6 ± 15.3 | 1.6 ± 0.85 | NA | NA | NA | NA |
| Würthwein et al. [91] | Allogeneic haematopoietic stem cell recipients (L-AMB) |
72 (44–105) | 3 mg/kg, median 10 days | 18.0 ± 8.6b | 6.5 ± 5.8b | 19.2 (9%) IIV: 38% |
1.22 (16%) IIV: 64% |
52.8 (29%) IIV: 84% |
2.18 (13%) IIV: 47% |
228 ± 159b | Terminal t ½: 54.3 |
| Nath et al. [136]c | Children with malignant disease (D-AMB) | 23.3 ± 1.3 | 1 mg/kg, up to 8 days | NA | NA | 8.51 (38%) | 0.79 (29%) | NA | NA | NA |
t
½,λ1: 1.46 ± 0.33 t ½,λ2: 26.4 ± 11.6 |
| Ohata et al. [93] | Patients with invasive fungal infection (L-AMB) |
27.1 ± 14.1 | 2.5 mg/kg loading dose Subsequently 1.0 or 5.0 mg/kg |
18.2 ± 11d (observed) 17.3 ± 7.6d (predicted) |
NA | 3.43 (19%)e
IIV: 100.2% |
0.255 (16%)e
IIV: 104.4% |
6.97 (29%)e
IIV: 238.5% |
0.661 (45%) | NA | NA |
| Lestner et al. [94] | Immunocompromised children (L-AMB) |
26.9 ± 14.0 | 2.5, 5.0, 7.5 or 10.0 mg/kg | NA | NA | Initialf: 10.7 (14.3%) Finalf: 2.3 (42.1%) |
0.67 L/h/70 kg | NA | NA | NA | NA |
Data given as either mean ± standard deviation, median (range) or mean (coefficient of variation %), unless indicated otherwise
AUC area under the concentration–time curve, CL clearance, C max peak plasma concentration, C trough trough plasma concentration 24 h after dose, D-AMB amphotericin B deoxycholate, IIV inter-individual variability, IOV inter-occasion variability, L-AMB liposomal amphotericin B, NA not available, Q intercompartmental clearance, t ½ plasma elimination half-life, t½,λ1 distributional half-life, t½,λ2 elimination half-life, V central volume of the central compartment, V peripheral volume of the peripheral compartment
aParameter scaled to a standardised weight of 21 kg
bAt steady state, exact definitions of C max and minimum concentration (C min) not provided in publication
cPosterior Bayesian estimates of the pharmacokinetic parameters for D-AMB, based on model including both D-AMB data and lipid emulsion data
dAfter single dose of 2.5 mg/kg daily
eParameter scaled to a standardised weight of 23 kg
fA decrease was identified in V central between the first and last day of treatment; these were estimated separately