Drug | Parameter | Wild-Type | BKO | PKO | TKO |
---|---|---|---|---|---|
Loperamide alone | t1/2 (h) | 1.85 | 1.7 | 7.8 | 5.6 |
CL (l/h)/kg | 2.9 | 2.6 | 1.2 | 1.8 | |
V (l/kg) | 6.6 | 7.0 | 10.6 | 10.1 | |
AUC0→∞ or (last) Plasma (h*ng)/ml | 1686 ± 413 | 1909 ± 312 | 4302 ± 781 | 2838 ± 273 | |
AUC0→∞ or (last) Brain (h*ng)/g | 173 ± 78 | 397 ± 105 | 17,503 ± 5100 | 13,832 ± 3503 | |
AUC0→∞ or (last) Spinal Cord (h*ng)/g | 70 ± 25 | 82 ± 9.6 | 8752 ± 1978 | 7823 ± 2403 | |
KpBrain | 0.10 | 0.21 | 4.1 | 4.9 | |
KpSpinal cord | 0.05 | 0.11 | 2.0 | 2.7 | |
Loperamide in combination | t1/2 (h) | 2.05 | 2.4 | 4.17 | 9.54 |
CL (l/h)/kg | 2.9 | 2.4 | 0.98 | 1.02 | |
V (l/kg) | 6.9 | 5.67 | 4.46 | 13.2 | |
AUC0→∞ or (last) Plasma (h*ng)/ml | 1744 ± 333 | 2080 ± 207 | 5266 ± 923 | 4860 ± 1377 | |
AUC0→∞ or (last) Brain (h*ng)/g | 460 ± 188 | 216 ± 27 | 13,350 ± 2012 | 14,566 ± 2713 | |
AUC0→∞ or (last) Spinal Cord (h*ng)/g | 90.2 ± 31.3 | 137 ± 26 | 10,516 ± 1966 | 9185 ± 1400 | |
KpBrain | 0.26 | 0.10 | 2.5 | 3.0 | |
KpSpinal cord | 0.05 | 0.07 | 2.0 | 1.89 |