Comparative pharmacokinetics and pharmacodynamics of a PEGylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children

Figures & data

Figure 1 Serum GH concentration after administration of rhGH (Jintropin AQ^®) and Jintrolong^®.

Notes: Serum GH concentration during the course of seven doses of Jintropin AQ^® administered once per day and the first dose of Jintrolong^® (PEG-GH) in children with GHD (A). Serum GH concentration during the course of six doses of Jintrolong^® administered weekly for 6 weeks in children with GHD (B).
Abbreviations: GH, growth hormone; PEG-GH, PEGylated growth hormone; GHD, growth hormone deficiency; rhGH, recombinant human growth hormone; h, hours; No, number.

Table 1 Pharmacokinetic parameters for rhGH and Jintrolong^®

	rhGH at 0.0286 mg/kg/d			Jintrolong^® at 0.2 mg/kg/w
	First dose	Seventh dose	P-value	First dose	Sixth dose	P-value
N	12	12		12	12
Cmax (ng/mL)	20.4±4.1	22.4±3.8	0.2283	327±70	340±44	0.5915
AUC0–168 h (ng·h/mL)	103±21	104±19	0.9428	34,837±8,235	37,229±7,911	0.5954
Tmax (hours)	3.8±0.5	3.8±0.8	0.7648	43.0±14.9	38.0±14.3	0.3594
t1/2 (hours)	2.3±0.4	2.3±0.8	0.9400	33.0±5.7	34.0±8.1	0.7933

Note: The results are expressed as the mean ± SD.

Abbreviations: rhGH, recombinant human growth hormone; AUC, area under the concentration vs time curve; N, number; C_max, maximal serum concentration; T_max, time of maximum concentration; t_1/2, half-life.

Table 2 The accumulated change in AUC (AUC_change) from baseline for serum IGF-1 during the course of seven doses of Jintropin AQ^® and the first and sixth doses of Jintrolong^® in children with GHD (n=12)

Group	Treatment	AUCtotal	AUCbaseline	AUCchange
rhGH	0.0286 mg/kg/d ×7	23,133.2±8,316.5	6,298.6±2,861.8	16,834.6±6,732.1
Jintrolong^® first	0.2 mg/kg/w	28,097.5±6,858.0	6,123.6±2,797.8	21,973.9±5,886.9
Jintrolong^® sixth	0.2 mg/kg/w	37,541.7±9,928.2	18,900.0±9,015.6	18,641.7±4,783.0

Note: The results are expressed as the mean ± SD.

Abbreviations: AUC, area under the concentration vs time curve; IGF-1, insulin-like growth factor-1; GHD, growth hormone deficiency; rhGH, recombinant human growth hormone.

Figure 2 Serum IGF-1 concentrations during the course of seven doses of Jintropin AQ^® administered once per day and the first and sixth doses of Jintrolong^® (PEG-GH) administered weekly in children with GHD (n=12).

Abbreviations: IGF-1, insulin-like growth factor-1; PEG-GH, PEGylated growth hormone; GHD, growth hormone deficiency; GH, growth hormone; No, number; h, hours.

Table 3 The accumulated change in AUC (AUC_change) from baseline for serum IGFBP-3 during the course of seven doses of Jintropin AQ^® and the first and sixth doses of Jintrolong^® in children with GHD (n=12)

Group	Treatment	AUCtotal	AUCbaseline	AUCchange
Jintropin AQ	0.0286 mg/kg/d ×7	473,209±64,179	287,994±67,577	190,879±66,043
Jintrolong first	0.2 mg/kg/w	490,046±64,813	250,320±65,448	239,726±86,217
Jintrolong sixth	0.2 mg/kg/w	615,947±66,064	505,120±96,408	110,827±53,186

Note: The results are expressed as the mean ± SD.

Abbreviations: AUC, area under the concentration vs time curve; IGFBP-3, insulin-like growth factor binding protein-3; GHD, growth hormone deficiency.

Figure 3 Serum IGFBP-3 concentrations during the course of seven doses Jintropin AQ^® administered once per day and the first and sixth doses of Jintrolong^® (PEG-GH) administered weekly in children with GHD (n=12).

Abbreviations: IGFBP-3, insulin-like growth factor binding protein-3; PEG-GH PEGylated growth hormone; GHD, growth hormone deficiency; GH, growth hormone; No, number; h, hours.

Table S1 Pharmacokinetic parameters for rhGH and Jintrolong^® in healthy adults

	Jintrolong^® (mg/kg/w)			rhGH (mg/kg/d)
	0.1	0.2	0.4	0.067
N	10	10	10	10
Sex	Male	Male	Male	Male
Cmax (ng/mL)	105.24±45.37	379.09±109.61	920.69±293.21	30.17±3.20
AUC0–t (ng·h/mL)	4,543.91±2,332.79	25,085.27±9,388.52	74,062.03±28,915.02	232.78±36.60
Tmax (hours)	22.20±9.82	29.40±10.75	40.80±8.39	3.2±1.1
t1/2 (hours)	31.70±4.70	32.19±4.58	30.39±5.93	1.95±0.44
MRT (hours)	40.86±9.18	49.90±7.53	60.92±7.29	6.20±0.39
Vd/F (mL/kg)	1,227.61±592.64	439.44±237.36	268.85±116.80	787.59±155.71
CL/F (mL/kg/h)	26.97±13.86	9.21±4.05	6.31±2.93	284.26±43.47

Note: The results are expressed as the mean ± SD.

Abbreviations: rhGH, recombinant human growth hormone; AUC, area under the concentration vs time curve; MRT, mean residence time; CL, clearance; h, hours; N, number; C_max, maximal serum concentration; T_max, time of maximum concentration; t_1/2, half-life; V_d/F, apparent volume of distribution; CL/F, apparent total clearance.