Table 1. Pharmacokinetics... | American Society of Hematology

Table 1.

Pharmacokinetics characterization of rD′D3-FP

Species	Treatment	CL, mL/h/kg	MRT, h	t_1/2, h
FVIII-ko mouse	rD′D3-FP (0.286-28.6 mg/kg, 100 IU/kg FVIII)	1.2 ± 0.4	61.0 ± 15.0	47.0 ± 13.0
	VWF (Haemate, 106 IU/kg FVIII, 290 IU/kg VWF)	23.6	1.8	5.1
	Fold difference	20*	34†	9†
VWF-ko mouse	rD′D3-FP (2.86 mg/kg, 100 IU/kg FVIII)	1.3	49.0	34.0
NMRI mouse	rD′D3-FP (2.86-28.6 mg/kg, 100 IU/kg FVIII)	2.4 ± 0.1	33.0 ± 4.0	26.0 ± 2.0
Rat	rD′D3-FP (0.14-28.6 mg/kg, 200 IU/kg FVIII); rD′D3-FP (2.86-28.6 mg/kg, 100, 300, 1000 IU/kg FVIII)	1.2 ± 0.1‡; 1.2 ± 0.1‡	55.1 ± 5.7‡; 59.5 ± 5.9‡	39.2 ± 3.9‡; 42.7 ± 4.2‡
	VWF (pdVWF, 400 IU/kg)	68.2	1.1	1.3
	Fold difference	59; 57	50†; 54*	30†; 33*
Rabbit	rD′D3-FP (1.4-8.6 mg/kg, 150 IU/kg FVIII)	0.5 ± 0.1	162.0 ± 17.0	112.0 ± 12.0
	VWF (pdVWF, 300 IU/kg)	22.2	4.0	4.2
	Fold difference	44*	41†	27†
Cynomolgus monkey	rD′D3-FP (7.15-28.6 mg/kg)	0.6-0.7	115.0-151.0	92.0-116.0
	VWF (pdVWF, 500 IU/kg)	5.21	15.5	11.3
	Fold difference	8-9*	7-10†	8-10†

Species	Treatment	CL, mL/h/kg	MRT, h	t_1/2, h
FVIII-ko mouse	rD′D3-FP (0.286-28.6 mg/kg, 100 IU/kg FVIII)	1.2 ± 0.4	61.0 ± 15.0	47.0 ± 13.0
	VWF (Haemate, 106 IU/kg FVIII, 290 IU/kg VWF)	23.6	1.8	5.1
	Fold difference	20*	34†	9†
VWF-ko mouse	rD′D3-FP (2.86 mg/kg, 100 IU/kg FVIII)	1.3	49.0	34.0
NMRI mouse	rD′D3-FP (2.86-28.6 mg/kg, 100 IU/kg FVIII)	2.4 ± 0.1	33.0 ± 4.0	26.0 ± 2.0
Rat	rD′D3-FP (0.14-28.6 mg/kg, 200 IU/kg FVIII); rD′D3-FP (2.86-28.6 mg/kg, 100, 300, 1000 IU/kg FVIII)	1.2 ± 0.1‡; 1.2 ± 0.1‡	55.1 ± 5.7‡; 59.5 ± 5.9‡	39.2 ± 3.9‡; 42.7 ± 4.2‡
	VWF (pdVWF, 400 IU/kg)	68.2	1.1	1.3
	Fold difference	59; 57	50†; 54*	30†; 33*
Rabbit	rD′D3-FP (1.4-8.6 mg/kg, 150 IU/kg FVIII)	0.5 ± 0.1	162.0 ± 17.0	112.0 ± 12.0
	VWF (pdVWF, 300 IU/kg)	22.2	4.0	4.2
	Fold difference	44*	41†	27†
Cynomolgus monkey	rD′D3-FP (7.15-28.6 mg/kg)	0.6-0.7	115.0-151.0	92.0-116.0
	VWF (pdVWF, 500 IU/kg)	5.21	15.5	11.3
	Fold difference	8-9*	7-10†	8-10†

Data are mean (± standard deviation) for mice and FVIII-competent rats, rabbits, and cynomolgus monkeys, as well as their improvement over human pdVWF.

CL, clearance.

Fold decrease.

†

Fold increase over human pdVWF.

‡

Two independent studies.

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