TABLE 2.
Estimates of values for pharmacokinetic parameters and their coefficients of variation and observed Cmax and Tmax values for different tissues after an intravenous bolus injection of AmB
| Tissue and pharmacokinetic parameter | Formulation (dose)
|
|||||
|---|---|---|---|---|---|---|
| Fungizone (1 mg/kg) | AmB-Nsp [125] (3 mg/kg) | AmB-Nsp [12.5] (3 mg/kg) | AmB-MM [125] (1 mg/kg) | AmB-MM [125] (3 mg/kg) | AmB-MM [12.5] (3 mg/kg) | |
| Liver | ||||||
| k13 = kk13 (h−1) | 4.4 (15)a | 5.5 (18) | 2.45 (15) | 9.7 (9) | 23.0 (10) | 2.3 (17) |
| k31 (h−1) | 4.13 (20) | 5.9 (22) | 1.13 (22) | 2.8 (14) | 4.2 (17) | 0.5 (24) |
| Tlag (h) | 3 | 3 | 3 | 3 | 3 | 3 |
| Cmax (μg/g) | 4.23 ± 1.20b | 9.23 ± 1.39 | 30.3 ± 2.29 | 12.5 ± 2.82 | 49.3 ± 6.33 | 42.5 ± 4.34 |
| Tmax (h) | 0.083 | 0.25 | 0.5 | 0.25 | 0.167 | 0.5 |
| Spleen | ||||||
| k13 = kk13 (h−1) | 6.6 (17) | 13.7 (18) | 6.9 (9) | 28 (37) | 15.3 (17) | 4.17 (9) |
| k31 (h−1) | 5.23 (20) | 5.58 (21) | 2.78 (13) | 12.2 (14) | 3.7 (20) | 0.99 (15) |
| Tlag (h) | 6 | 3 | 3 | 10 | 10 | 10 |
| Cmax (μg/g) | 4.30 ± 0.18 | 31.3 ± 1.52 | 50.6 ± 13.4 | 19.9 ± 4.71 | 53.9 ± 7.29 | 37.7 ± 3.90 |
| Tmax (h) | 0.25 | 0.5 | 0.167 | 0.083 | 0.25 | 1 |
| Kidney | ||||||
| k13 (h−1) | 4.61 (13) | 1.99 (15) | 0.6 (13) | 1.95 (15) | 1.5 (16) | 0.3 (17) |
| k31 (h−1) | 4.42 (17) | 1.35 (22) | 0.3 (23) | 0.76 (22) | 0.42 (20) | 0.08 (27) |
| AUC1 (μg · h/g) | 20.58 (11) | 96.32 (21) | 163.9 (8) | 162.6 (11) | 207.8 (13) | 206.3 (6) |
| Cmax (μg/g) | 2.4 ± 0.34 | 9.2 ± 0.07 | 9.11 ± 0.95 | 5.71 ± 0.59 | 9.25 ± 0.29 | 6.5 ± 0.50 |
| Tmax (h) | 0.25 | 0.5 | 1 | 3 | 6 | 0.167 |
a
Values in parentheses are coefficients of variation (in percent).
b
Mean ± standard deviation.