Summary pharmacokinetic parameters determined by noncompartmental analysis of total drug concentrations of OMI in WT, BKO, PKO, and TKO FVB mice after a single intravenous dose (5 mg/kg) and after coadministration with loperamide (5 mg/kg)
A two-tailed unpaired t test was performed to compare AUCs among tissues within the same study (see results) and between the same tissues in discrete vs. combination studies. A one-way ANOVA with Tukey’s multiple comparisons test was used to compare AUCs for the same tissue among different genotypes. Results are presented as mean or mean ± S.D.
| Drug | Parameter | Wild-Type | BKO | PKO | TKO |
|---|---|---|---|---|---|
| OMI alone | t1/2 (h) | 2.9 | 2.9 | 2.6 | 2.8 |
| CL (l/h)/kg | 9.8 | 8.0 | 6.7 | 7.4 | |
| V (l/kg) | 24.9 | 16.6 | 15.5 | 15.5 | |
| AUC0→∞ or (last) Plasma (h*ng)/ml | 508 ± 57 | 623 ± 86 | 735 ± 43 | 670 ± 42 | |
| AUC0→∞ or (last) Brain (h*ng)/g | 500 ± 116 | 760 ± 66 | 5976 ± 184 | 5665 ± 159 | |
| AUC0→∞ or (last) Spinal Cord (h*ng)/g | 172 ± 16 | 121 ± 27 | 5689 ± 607 | 2952 ± 62 | |
| KpBrain | 1.0 | 1.2 | 8.1 | 8.4 | |
| KpSpinal cord | 0.34 | 0.18 | 7.6 | 4.3 | |
| OMI in combination | t1/2 (h) | 2.5 | 2.6 | 3.48 | 3.37 |
| CL (l/h)/kg | 5.0 | 3.0 | 1.8 | 2.6 | |
| V (l/kg) | 13 | 8.7 | 5.8 | 10.1 | |
| AUC0→∞ or (last) Plasma (h*ng)/ml | 1002 ± 167 | 1541 ± 245 | 2613 ± 258 | 1893 ± 130 | |
| AUC0→∞ or (last) Brain (h*ng)/g | 1115 ± 136 | 1076 ± 77 | 6993 ± 581 | 7128 ± 458 | |
| AUC0→∞ or (last) Spinal Cord (h*ng)/g | 326 ± 71 | 248 ± 32 | 3584 ± 260 | 3913 ± 203 | |
| KpBrain | 1.1 | 0.71 | 2.7 | 3.7 | |
| KpSpinal cord | 0.33 | 0.16 | 1.37 | 2.0 |