TABLE 2.
Pharmacokinetic parameters of drug in plasma and whole blood (for ABLC) after administration of multiple intravenous doses of Doc-AmB and ABLC to regular diet-fed and cholesterol-fed rabbitsa
| Experimental group and drug | AUC0–∞ (μg · h/ml) | t1/2α (h) | t1/2β (h) | MRT (h) | Vss (liters/kg) | CL (ml/h/kg) |
|---|---|---|---|---|---|---|
| Regular diet | ||||||
| Doc-AmB (plasma) | 35.3 ± 9.2 | 4.4 ± 1.8 | 101.4 ± 20.8 | 141 ± 26 | 4.4 ± 2.1 | 30.1 ± 8.9 |
| ABLC (plasma) | 2.6 ± 1.2c | 0.3 ± 0.1c | 87.1 ± 35.4c | 126 ± 51 | 50 ± 9c | 475 ± 259c |
| ABLC (whole blood) | 18.1 ± 3.2cd | 1.8 ± 0.3cd | 641.6 ± 139.5cd | 920 ± 203cd | 52 ± 14c | 56.6 ± 11cd |
| Cholesterol-enriched diet | ||||||
| Doc-AmB (plasma) | 140.4 ± 32.8b | 4.9 ± 2.3 | 110.3 ± 28.1 | 152 ± 38 | 1.1 ± 0.3b | 7.5 ± 2.0b |
| ABLC (plasma) | 10.0 ± 3.9bc | 4.3 ± 3.9b | 209.0 ± 107.8 | 297 ± 159b | 29 ± 11c | 104 ± 24bc |
| ABLC (whole blood) | 90.5 ± 65.9bd | 2.4 ± 0.3 | 2,623 ± 2,466 | 3,754 ± 3,544c | 39 ± 11c | 19.4 ± 18.6b |
a
By these regimens the animals each received 1 mg of AmB per kg. The cholesterol enrichment contained 0.5% (wt/vol) cholesterol. Data are expressed as means ± standard deviations (n = 4 for Doc-AmB in plasma, n = 5 for ABLC in plasma, and n = 3 for ABLC in whole blood). t1/2α and t1/2β, α and terminal half-lives, respectively.
b
P < 0.05 versus rabbits fed a regular diet.
c
P < 0.05 versus Doc-AmB treatment.
d
P < 0.05 versus ABLC (plasma).