Table 3

Repeat-dose administration of oral THU-DAC in 4 baboons: effects on HbF percentage and neutrophil and platelet counts

Baboon no.DAC dose, mg/m2*SchedulePretreatment HbF, %Peak HbF, %ΔHbFANC nadir, ×109/LPlatelet count maximum, ×109/L
7470 2×/wk for 8 wks 9.9 29.3 29.3 2.13 895 
7472 2×/wk for 8 wks 12.8 30.1 30.1 1.46 600 
7482 10 3×/wk for 3 wks 2×/wk for 5 wks 3.5 23.8 20.3 2.58 1004 
7484 10 2×/wk for 8 wks 4.2 23.1 23.1 1.68 1029 
Baboon no.DAC dose, mg/m2*SchedulePretreatment HbF, %Peak HbF, %ΔHbFANC nadir, ×109/LPlatelet count maximum, ×109/L
7470 2×/wk for 8 wks 9.9 29.3 29.3 2.13 895 
7472 2×/wk for 8 wks 12.8 30.1 30.1 1.46 600 
7482 10 3×/wk for 3 wks 2×/wk for 5 wks 3.5 23.8 20.3 2.58 1004 
7484 10 2×/wk for 8 wks 4.2 23.1 23.1 1.68 1029 

Two of these animals had relatively low bioavailability (baboons PA7472 and PA7482) and 2 had relatively high oral THU-DAC bioavailability (baboons PA7484 and PA7470) according to the pharmacokinetic studies.

ANC indicates absolute neutrophil count.

*

Administered after THU 400 mg/m2.

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