Table 4.
Tissue levels of IFG.
Species | IFG tartrate (mg/kg) | Tissue | [IFG] (ng/g or ng/mL) | LOQ (ng/g or ng/mL) | |
---|---|---|---|---|---|
Day 0 | Day 2 | ||||
L444P GCase mice | 20 | Plasma | 71±7 | <LOQ | 5 |
Liver | 177±17 | <LOQ | 20 | ||
Spleen | 70±4 | <LOQ | 20 | ||
Lung | 69±10 | <LOQ | 20 | ||
Brain | <LOQ | <LOQ | 50 | ||
Monkey | 1000 | CSF | 673±128 | ND | 100 |
Four-month old L444P GCase mice were administered IFG tartrate (20 mg/kg per day, equivalent to 10 mg/kg free base) ad libitum in drinking water for four weeks. Mice were euthanized on the last day of dosing (Day 0) or two days after IFG tartrate withdrawal (Day 2). For monkeys (Cynomolgus), a single dose of IFG tartrate (1000 mg/kg, equivalent to 500 mg/kg free base) was administered by oral gavage with cerebrospinal fluid collected two hours post-administration. IFG levels were quantitated by LC-MS/MS and expressed as ng/mL (plasma and CSF) or ng/g (liver, spleen, lung, and brain). Values represent the mean±SEM for groups of 6 (L444P GCase mice) or 10 (monkeys). LOQ, limit of quantitation.