Table 2. Population PK parameter... | American Society of Hematology

Table 2.

Population PK parameter estimates

	Nonbleeding	Bleeding
CL_tot,pop (mL/h per 70 kg)(CL_NL,pop. CL_L,pop)
1st dose	58.5 (31.3-27.2)	87.2 (60.0, 27.2 fixed)
2nd to <5th dose	44.7 (17.5-27.2)
≥5th dose	41.6 (14.4-27.2)
Vd_pop (L/70 kg)
1st dose	5.5	4.4
2nd to <5th dose	6.5
≥5th dose	8.0
Exponent for predose sC5b-9	0.53	0.52
Exponent for body weight	0.97 for CL0.63 for Vd	1.03 for CL0.74 for Vd
Interindividual variability	44.7% for CL33.6% for Vd	31.6% for CL34.5% for Vd
Residual proportional variability	0.11	0.084

	Nonbleeding	Bleeding
CL_tot,pop (mL/h per 70 kg)(CL_NL,pop. CL_L,pop)
1st dose	58.5 (31.3-27.2)	87.2 (60.0, 27.2 fixed)
2nd to <5th dose	44.7 (17.5-27.2)
≥5th dose	41.6 (14.4-27.2)
Vd_pop (L/70 kg)
1st dose	5.5	4.4
2nd to <5th dose	6.5
≥5th dose	8.0
Exponent for predose sC5b-9	0.53	0.52
Exponent for body weight	0.97 for CL0.63 for Vd	1.03 for CL0.74 for Vd
Interindividual variability	44.7% for CL33.6% for Vd	31.6% for CL34.5% for Vd
Residual proportional variability	0.11	0.084

The final model for nonbleeding patients is as follows: $CL = {CL}_{L} + {CL}_{NL}, {CL}_{L} = {CL}_{L, pop} \times {(WT / 70)}^{0.97}, {CL}_{NL} = {CL}_{NL, pop} \times {(sC5b - 9 / 244)}^{0.53} \times {(WT / 70)}^{0.97}, Vd = {Vd}_{pop} \times {(WT / 70)}^{0.63}$ ⁠.

Final model for bleeding patients is as follows: $CL = {CL}_{L} + {CL}_{NL}, {CL}_{L} = {CL}_{L, pop} \times {(WT / 70)}^{1.03}, {CL}_{NL} = {CL}_{NL, pop} \times {(sC5b - 9 / 244)}^{0.52} x {(WT / 70)}^{1.03}, Vd = {Vd}_{pop} \times {(WT / 70)}^{0.74}$ ⁠.

where CLNL,pop is the eculizumab population mean nonlinear clearance for a 70-kg patient; CLL_pop, is the eculizumab population mean linear clearance for a 70-kg patient; CL_tot,pop is the population mean total clearance defined as sum of CLNL_pop and CLL_pop; Vd_pop, is the population mean volume of distribution for a 70-kg patient; and WT is actual body weight (in kilograms).

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