Table 4.
Pharmacokinetic Coefficients of Unconjugated and Conjugated PNA in Mouse Organs/Tissues after Oral Administration: Half-Times of Biphasic Clearance Pattern
| |
Half-time of rapid clearance T1 (hours) |
Half-time of slow clearance T2 (hours) |
||||
|---|---|---|---|---|---|---|
| Organ/Tissues | PNATAR | PNATAR-Penetratin (S-S) | PNATAR-Penetratin (-O-) | PNATAR | PNATAR-Penetratin (S-S) | PNATAR-Penetratin (-O-) |
| Kidney | 0.5 (±0.1) | 0.8 (±0.31) | 0.7 (±0.1) | 51.0 (±116) | 495.0 (±2581) | 330.0 (±2389) |
| Intestine | 0.5 (±0.1) | 1.5 (±0.46) | 0.7 (±0.1) | 187.0 (±334) | 169.0 (±58) | 277.0 (±255) |
| Stomach | 0.8 (±0.2) | 2.9 (±0.73) | 0.5 (±0.1) | 65.0 (±12) | 63.0 (±20) | 136.0 (±109) |
| Liver | 0.5 (±0.1) | 1.3 (±0.24) | 0.7 (±0.1) | 30.0 (±22) | 99.0 (±100) | 866.0 (±5739) |
| Spleen | 0.6 (±0.1) | 1.7 (±0.15) | 1.0 (±0.1) | X | X | 2.0 (x) |
| Blood | 0.5 (±0.1) | 1.5 (±0.19) | 0.8 (±0.1) | X | 72.0 (±73) | 27.0 (±9.0) |
| Lungs | 0.5 (±0.1) | 0.9 (±0.07) | 0.8 (±0.1) | 38.0 (±40) | 40.0 (±22) | 102.0 (±184) |
| Brain | 0.5 (±0.1) | 1.3 (±0.50) | 0.4 (±0.2) | X | 26.0 (±23) | 28.0 (x) |
| Heart | 0.6 (±0.1) | 1.5 (±0.15) | 1.1 (±0.3) | X | 23.0 (±12) | 8.1 (±3.6) |
| Sk Muscle | 0.9 (±0.1) | 2.0 (±0.20) | 1.1 (±0.1) | X | X | 24.0 (x) |
The half-time of the biphasic clearance pattern, comprised of a fast-release (T1) and slow-release component (T2). For each time point, four mice were injected. The values in italics in parenthesis are the results of uncertainties in the fitting procedure by a two-component function, as noted in the Results. The goodness of fit (R2) values ranged from 0.85 to 1. Each “X” indicates that, in the specified organs or tissues, no significant data could be obtained to determine b and T2 values for PNATAR and its CPP conjugates.