TABLE 2

Summary PK parameters based on simulated and observed plasma concentrations following the oral administration of R-PZQ ODTs and rac-PZQ ODTs

Geometric mean (Geometric CV, %) values are reported. Simulations were performed using the Vmax and Km in rhP450s generated by the substrate depletion method to describe metabolism. In vitro-in vivo extrapolation (IVIVE) scaling was performed using the reference compound scaling approach.

R-PZQ Parameters after Administration of R-PZQ ODTsa
R-PZQ dose (mg/kg)SimulatedObserved
AUC(0,24) (h⋅ng/ml)CLpo (l/h)Cmax (ng/ml)AUC(0,24) (h⋅ng/ml)CLpo (l/h)Cmax (ng/ml)
10205(70)3305(70)78(74)188(109)3091(93)90.9(93)
20467(71)2882(72)177(75)813(103)1665(94)389(113)
30694(69)2910(69)264(74)2307(78)924(71)1067(84)
R-PZQ Parameters after Administration of rac-PZQ ODTs
rac-PZQ dose (mg/kg)SimulatedObserved
AUC(0,24) (h⋅ng/ml)CLpo (l/h)Cmax (ng/ml)AUC(0,24) (h⋅ng/ml)CLpo (l/h)Cmax (ng/ml)
201565(71)420(70)553(68)331(74)2157(63)157(83)
404033(71)336(73)1432(66)2067(46)697(44)885(57)
605853(75)340(73)2142(72)4955(41)435(45)1562(32)
S-PZQ Parameters after Administration of rac-PZQ ODTs
rac-PZQ dose (mg/kg)SimulatedObserved
AUC(0,24) (h⋅ng/ml)CLpo (l/h)Cmax (ng/ml)AUC(0,24) (h⋅ng/ml)CLpo (l/h)Cmax (ng/ml)
201481(85)444(83)532(80)2278(46)313(47)797(41)
404116(87)329(90)1476(78)7783(28)185(32)2347(31)
605825(90)341(88)2177(83)14,832(34)145(40)3263(20)
  • AUC(0,24), area under the concentration-time curve from 0 to 24 hours after dosing; CLpo, oral clearance.