Table 1.

Pharmacokinetic study of NXD30001 in mice

(A) Pharmacokinetic profile
AUC(0-t)Cmax (ng/g)C0 (ng/mL)Tmax (h)T1/2 (h)CL (mL/min/kg)Vd (L/kg)Ratio of AUC(0-t) (brain/plasma)
Single dose
    Plasma (ng.h/mL)5,346NA2,140NA2.7421751.5NA
    Brain (ng.h/g)1,073223NA0.54.07NANA0.201
Repeated doses
    Plasma (ng.h/mL)6,960NA4,530*NA5.459.827.9NA
    Brain (ng.h/g)940210NA0.258.99NANA0.135
(B) Brain concentrations
Time (h)NXD30001 (ng/g)17-AAG (ng/g)
100 mg/kg150 mg/kg75 mg/kg
6675.51439.52.6
128233424ND
24271899.5ND
4810.7115.5ND

NOTE: (A) Concentrations of NXD30001 in plasma and brain homogenates were determined by LC/MS-MS after a single i.v. injection at 70 mg/kg or after repeated i.v. injections at 25 mg/kg every other day for a total of 7 doses.

(B) Brain concentrations of HSP90 inhibitors in mice. Concentrations of NXD30001 and 17-AAG in brain homogenates were determined by LC/MS-MS after a single i.p injection.

Abbreviations: AUC0-t, area under the curve from the time of dosing to the time of the last observation; Cmax, maximum concentration; C0, concentration at time 0; Tmax, time of the maximum concentration; T1/2, terminal half-life; CL, clearance; Vd, volume of distribution at terminal phase; NA; not applicable; ND; not detected.

  • * The concentration shown is the average concentration at 0.5 hour rather than C0.