Table II.
Pharmacokinetic Parameters in Rats After Intratracheal Administration of Developed BUD Formulations
| Pharmacokinetic parameters | Intratracheal administration (n = 4) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Conventional formulation (batch L2) | Microspheres formulation (batch CH3) | Porous particles formulation (batch PC1) | |||||||
| Plasma | Lungs | BALF | Plasma | Lungs | BALF | Plasma | Lungs | BALF | |
| Ka (h−1) | 0.31 | 0.07 | 0.08 | 0.29 | 0.33 | 0.33 | 2.26 | 0.66 | 1.29 |
| T 1/2(Ka) (h) | 2.23 | 9.64 | 8.18 | 2.37 | 2.10 | 2.09 | 0.31 | 1.04 | 0.54 |
| Ke (h−1) | 0.07 | 0.06 | 0.06 | 0.08 | 0.04 | 0.06 | 0.050 | 0.13 | 0.03 |
| T 1/2(Ke) (h) | 9.04 | 12.52 | 11.22 | 9.42 | 15.61 | 11.28 | 14.00 | 5.45 | 22.77 |
| T max (h) | 1.0 | 0.5 | 2.0 | 2.0 | 0.5 | 2.0 | 3.0 | 1.0 | 1.0 |
| C max (ng/ml) | 3.95 | 1.54 | 0.97 | 4.19 | 3.04 | 0.50 | 10.49 | 5.43 | 1.15 |
| AUC0–4 h (ng h/ml) | 6.12 | 3.24 | 2.01 | 8.78 | 3.32 | 1.34 | 24.15 | 11.29 | 4.11 |
| Vd (L) | 0.81 | 2.08 | 3.31 | 0.76 | 1.05 | 4.19 | 0.31 | 0.59 | 0.88 |
| Relative bioavailability (F) | – | 0.65 (1.2-fold compared to conventional formulation) | 1.92 (3.5-fold compared to conventional formulation) | ||||||
Ka absorption rate constant, T 1/2 half life, Ke elimination rate constant, T max time required to reach maximum concentration, C max concentration maximum, AUC area under the curve, Vd apparent volume of distribution