Table 3.

Parameter estimates. Final pharmacodynamic model

Parameter	Description	Estimate (95% CI)	RSE (%)	IIV CV (%)	Shrinkage (%)
$K_{\text{in}}$ (ng/mL/h)	Zero-order production rate of IGF-I at zero GH levels (estimated)	0.949 (0.411–1.49)	28.9	117	15.1
$K_{{\text{in,endo}}_{\text{adult}}}$ (ng/mL/h)	Zero-order production rate of IGF-I at endogenous GH levels for 85-kg adults with GHD (derived)	1.97	–	–	–
$K_{{\text{in,endo}}_{\text{child}}}$ (ng/mL/h)	Zero-order production rate of IGF-I at endogenous GH levels for 25-kg children with GHD (derived)	2.22	–	–	–
$K_{\text{out}}$ (1/h)	First-order elimination rate of IGF-I	0.0262 (0.0218–0.0306)	8.6	17.4	31.3
${\text{EC}}_{50}$ (ng/mL)	Somatropin concentration corresponding to half-maximum stimulation of IGF-I production rate	2.13 (1.39–2.88)	17.9
$E_{{\text{max}}_{\text{adult}}}$ (ng/mL/h)	Maximum increase in IGF-I production rate for adults with GHD	15.1 (fixed)	–	33.1	13.3
${\theta }_{{\text{BW}}_{E_{{\max }_{\text{adult}}}}}$	Body weight covariate on the maximum increase in IGF-I production rate for adults with GHD	0.46 (fixed)	–	–	–
$E_{{\text{max}}_{\text{child}}}$ (ng/mL/h)	Maximum increase in IGF-I production rate for children with GHD	6.48 (4.75–8.70)	14.0	33.1	13.3
${\theta }_{{\text{BW}}_{E_{{\max }_{\text{child}}}}}$	Body weight covariate on the maximum increase in IGF-I production rate for children with GHD	1.94 (1.05–2.84)	23.5	–	–
Proportional error Trial 1 (%)	–	14.6	–	–	9.4
Proportional error Trial 2 (%)	–	8.7	–	–	5.5
Proportional error Trial 3 (%)	–	11.4	–	–	12.0

BW body weight, CI confidence interval, CV coefficient of variation, E_max maximum increase in IGF-I production rate, EC₅₀ GH concentration corresponding to half-maximum stimulation of IGF-I production rate, GH growth hormone, GHD growth hormone deficiency, IGF-I insulin-like growth factor-I, IIV inter-individual variability, K_endo zero-order process for endogenous growth hormone production, K_in zero order production rate of IGF-I, K_out first-order elimination rate of IGF-I, RSE relative standard error