Table 9.
Brain penetration of tramiprosate after single-dose oral administration of tramiprosate and ALZ-801 in rodents
| A. Brain and plasma levels of radioactivity after a single oral dose of 14C-tramiprosate (100 or 500 mg/kg) in male C57BL/6 mice. N = 3 per dose/sampling time points; mean PK curves were used for calculation of PK parameters. Brains were perfused prior to bioanalysis | ||||||
|---|---|---|---|---|---|---|
| Tissue | Dose (mg/kg) | C max (µg eq/mL) | T max (h) | AUCt (µg eq/mL h) | AUCinf (µg eq/mL h) | t ½ (h) |
| Plasma | 100 | 8.01 | 2 | 68.8 | 69.3 | 3.28 |
| 500 | 28.9 | 4 | 388 | 397 | 4.43 | |
| Brain | 100 | 0.741 | 8 | 13.2 | 26.1 | 20.6 |
| 500 | 3.64 | 12 | 63.0 | NC | NC | |
| B. Comparison of brain and plasma tramiprosate exposure (mean AUCt; ng/ml h) after a single oral dose of ALZ-801 vs. tramiprosate (equivalent dose) in male CD-1 mice. N = 6 per group/sampling time points; mean PK curves were used for calculation of PK parameters. Drug concentrations were measured using an LC-MS method | |||
|---|---|---|---|
| Tissue | ALZ-801 dose (172 mg/kg) | Tramiprosate dose (100 mg/kg) | ALZ-801:tramiprosate ratio |
| Plasma | 58,758 | 32,274 | 1.8 |
| Brain | 5841 | 1861 | 3.1 |
PK pharmacokinetic, C max maximum concentration, T max time to reach Cmax, AUC t area under the concentration–time curve from time zero to time t, AUC inf area under the concentration–time curve from time zero to infinity, t ½ half-life, LC-MS liquid chromatography-mass spectrometry, NC not calculated; terminal mono-exponential phase contained only two points