TABLE 3.
Pharmacokinetic parameters determined in mice for NP10679.
| Oral Bioavailability | Intraperitoneal Dosing | Brain:Plasma Ratiosa | |||||
|---|---|---|---|---|---|---|---|
| Species | Mouse BALB/c | Mouse BALB/c | Mouse BALB/c | ||||
| Dose (mg/kg) | 10 | 3 | 2 | 5 | 3 | ||
| Route | Oral | i.v. | i.p. | i.p. | i.v. | ||
| Studyb | 3 | 3 | 4 | 4 | 1 | 2A | 2B |
| Plasma Cmax (ng/ml) | 3600 | 2350 | 581 | 1470 | 1740 | 600 | 817 |
| Plasma Tmax (h) | 1.0 | 0.08 | 0.5 | 0.5 | 1.0 | 1.0 | 1.0 |
| Brain conc. (ng/g) | — | — | — | — | 2300 | 1420 | 2100 |
| Brain:plasma ratio | — | — | — | — | 1.3 | 2.4 | 2.6 |
| Plasma AUClast (h*ng/ml) (0–24 h) | 45,000 | 17,800 | 4750 | 11,800 | — | — | — |
| Plasma AUCinf (h*ng/ml) | 49,500 | — | 5690 | 13,100 | — | — | — |
| Plasma AUCextrap (%) | 9.18 | — | 16.6 | 9.8 | — | — | — |
| Plasma T1/2 (h) | 7.06 | 8.56 | 9.9 | 7.5 | — | — | — |
| Plasma MRTlast | 7.16 | 7.08 | 7.5 | 6.7 | — | — | — |
| Vss (L/kg) | — | 1.59 | — | — | — | — | — |
| CL (ml/min per kilogram) | — | 2.44 | — | — | — | — | — |
| Bioavailability (F %) | 75.7 | — | — | — | — | — | — |
aBrain:plasma ratio studies reported only at 1 h.
bAll studies used 10% DMA/10% PG/30% HPBCD/50% sterile water formulation, except study 2B, which used 2% DMA/10% PG/30% HPBCD/58% sterile water. T1/2, elimination half-life; AUClast, area under the plasma concentration-time curve from time zero to last measurement; AUCinf, area under the plasma concentration-time curve from time zero to infinity; AUCextrap, area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC; MRTlast, mean residence time from time zero to last measurement; Vss, apparent volume of distribution at steady state; CL, apparent total body clearance of drug from plasma. A dash ( - ) indicates that parameter not determined.