Table 1 Dosing regimens for LRRK2 inhibitors and associated plasma exposures.

The dosing regimen for each compound was selected on the basis of PK-PD studies conducted by the pharmaceutical companies. Expected versus observed exposure multiples for each test compound are shown.

Test compounds
(group #)
VehicleMouse brain
unbound IC50
(nM) for pSer935
inhibition
Animals per groupDoses tested
(mg/kg, PO) and
[targeted
exposure
multiples]
Observed exposure multiples
MaleFemaleMaleFemale
Vehicle (group 1)1% (w/v) Avicel
RC591 and 0.2%
(v/v) polysorbate
80 (Tween 80) in
reverse osmosis
water
NA22NANANA
2*2*
GNE-7915 (groups
2 and 3)
Embedded Image
1% (w/v) Avicel
RC591, 0.2% (v/v)
polysorbate 80
(Tween 80) in
reverse osmosis
water
972230 (BID) [1×]3.2×2.0×
2*2*
MLi-2 (groups 3
and 4)
Embedded Image
0.5% (w/v)
Methocel A4C
Premium in 10
mM citrate
buffer, pH 4.0, in
reverse-osmosis
water
0.82215 (QD) [1×]9.5×16.9×
2250 (QD) [10×]45.5×64.8×
PFE-360 (groups 5
and 6)
Embedded Image
1.25% (w/w)
hydroxypropyl
cellulose 0.05%
(w/w) docusate
sodium in
deionized water
3.0223 (QD) [1×]1.2×
226 (QD) [10×]10.2×8.1×

*Number of animals used to assess recovery.