Table 1.
Pharmacokinetic Coefficients of Unconjugated and Conjugated PNA in Mouse Organs/Tissues after IP Administration: Accumulation of Rapid and Slow Clearance Components
| |
Accumulation of rapid clearance component a (%AA/g) |
Accumulation of slow clearance component b (%AA/g) |
||||
|---|---|---|---|---|---|---|
| Organ/Tissues | PNATAR | PNATAR-Tat | PNATAR-Penetratin | PNATAR | PNATAR-Tat | PNATAR-Penetratin |
| Kidney | 8.70 (±3.6) | 5.77 (±5.0) | 3.90 (±0.7) | 13.37 (±0.59) | 14.73 (±1.72) | 2.7 (±0.33) |
| Intestine | 18.45 (±1.6) | 4.73 (±1.2) | 12.00 (±5.0) | 0.13 (±0.01) | 0.26 (±0.19) | 0.18 (±0.07) |
| Liver | 1.16 (±0.3) | 1.99 (±0.8) | 2.40 (±0.45) | 0.24 (±0.04) | 0.46 (±0.22) | 0.32 (±0.08) |
| Blood | 2.47 (±1.2) | 3.94 (±2.4) | 4.10 (±0.95) | 0.53 (±0.30) | 0.12 (±0.01) | 0.08 (±0.10) |
| Spleen | 4.27 (±0.6) | 1.57 (±0.6) | 0.88 (±0.23) | 0.28 (±0.07) | 0.39 (±0.09) | 0.26 (±0.07) |
| Heart | 0.91 (±0.2) | 1.30 (±0.2) | 0.79 (±0.18) | 0.05 (±0.0X) | 0.16 (±0.05) | 0.07 (±0.01) |
| Brain | 0.09 (±0.03) | 0.14 (±0.05) | 0.14 (±0.10) | 0.01 (±0.0X) | 0.03 (±0.004) | 0.014 (±0.008) |
| Lungs | 3.76 (±0.7) | 3.83 (±0.30) | 0.93 (±0.28) | 0.07 (±0.0X) | 0.26 (±0.08) | 0.07 (±0.01) |
| Skeletal muscle | 0.36 (±0.1) | 0.88 (±0.30) | 2.50 (±0.30) | 0.13 (±0.01) | 0.16 (±0.04) | 0.07 (±0.02) |
A single dose of 125I-labeled PNA was IP administered to Balb/C mice as described in Materials and Methods. Mice were euthanized at different time points and the radioactive PNA compounds in different organs and tissues were monitored. Accumulation of radioactivity in individual organs or tissues was calculated as a percent of injected activity per gram tissue (%IA/g). Maximum accumulation is expressed as a percent of injected activity per gram (%IA/g). a = pharmacokinetic coefficient for maximum accumulation by the rapid-release pathway; b = pharmacokinetic coefficient for maximum accumulation by the slow-release pathway.