ISSN:1663-2818    

DOI:10.1159/000182367

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The pharmacokinetics and acute effects of an authentic recombinant DNA-derived human growth hormone (rhGH) produced by genetically engineered mammalian cells were determined in 12 healthy volunteers following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of 4IU (1.3 mg) hGH/m2 body surface area. Following i.v. administration, apparent elimination half-life of rhGH was 18 min. Following i.m. administration, a mean peak serum concentration of 36.9 ng/ml (range 13-61 ng/ml) occurred at 3 h, and following s.c. administration, more sustained but lower serum concentrations occurred, with mean peak concentrations of 16.4 and 16.3 ng/ml at 4 and 6 h (ranges 9.0-27.5 ng/ml and 6.5-35.5 ng/ml at 4 and 6 h, respectively). The mean area under the curves was lower after s.c. (134 ± 48 ng·h·mH) than after i.m. (194 ± 48 ng·h·ml-1) injections (p < 0.03). Comparable results were obtained for the same dose of rhGH given subcutaneously in concentrations of either 4 IU/ml or 10 IU/ml. Both i.m. and s.c. administrations caused similar increases in free fatty acids at 4 h and insulin-like growth factor I at 24 h. Insulin, C-peptide and blood glucose were almost unchanged during the first 4 h after administration, whereas leukocytes increased significantly (p < 0.0001). Local and systemic tolerance were good, and no adverse reactions were observed. In a GH-deficient child, hGH serum levels between 10 and 20 ng/ml were demonstrated for a period of 8 h after s.c. administration of 0.07 IU rhGH/kg body w

ISSN:1663-2818    

DOI:10.1159/000182369

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effect of a mammalian-cell-derived recombinant human growth hormone (rhGH) on nitrogen and whole-body protein metabolism was assessed in 12 children with complete growth hormone (GH) deficiency. All the patients received single oral doses of 15N-glycine (95 atom % 15N), 20 mg/kg body weight, prior to and following 7 days of treatment with rhGH, 1.7 IU/m2 body surface area (BSA) per day, administered subcutaneously. Prior to rhGH, mean urinary 15N-nitrogen excretion was 42.8 ± 8% of the administered dose, which fell significantly to 22.8 ± 7% during rhGH administration (p < 0.0001). Stimulation of protein metabolism by rhGH resulted in a protein net gain rate of 1.1 ± 0.4 g/kg/day, which was significantly higher than the 0.6 ± 0.5 g/kg/day rate seen prior to rhGH (p < 0.001). In patients subsequently placed on daily subcutaneous injections of rhGH 1.7 IU/m2 BSA, mean height velocity standard deviation score (HV SDS) for chronological age significantly increased from-3.8 ± 2.6 to+8.5 ± 3.1 and+3.3 ± 2.2, during the 1st and 2nd years of treatment, respectively. However, there was no correlation between the long-term response to rhGH treatment and the short-term changes in nitrogen or protein metabolism in GH-deficient ch

ISSN:1663-2818    

DOI:10.1159/000182372

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

A total of 17 patients (14 boys, 3 girls) with poor growth due to idiopathic growth hormone deficiency (IGHD) were treated for 12 months with recombinant human growth hormone (rhGH; Saizen), 0.5 IU/kg body weight per week administered by subcutaneous injection on a daily basis. Therapy significantly increased growth velocity (GV) from 4.0 ± 1.5 to 10.1 ± 2.4 cm/year (p < 0.001). Correspondingly, GV standard deviation score (GV SDS) for chronological age (CA) increased from -2.7 ± 1.6 to +4.5 ± 2.8; GV SDS for bone age (BA) increased from -4.0 ± 2.0 to +3.6 ± 3.3; and patient height SDS-CA increased from -3.5 ± 1.1 to -2.4 ± 0.7. Changes in these parameters were significant at p < 0.001. During the course of the study, mean plasma IGF-1 levels rose significantly from 0.3 ± 0.2 IU/ml to 1.3 ± 1.2 IU/ml(p < 0.01). BA maturation proceeded at approximately 1 year per treatment year. Therapy was well tolerated. Anti-hGH antibodies were seen in only 1 patient at a low concentration, and did not appear to affect GV. This study demonstrates that rhGH is safe and efficacious when used to increase height in patients

ISSN:1663-2818    

DOI:10.1159/000182374

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In five clinical studies performed in Austria, France, the FRG, Italy, Switzerland, the UK and the USA, 304 growth hormone (GH)-deficient children were treated with recombinant human GH (rhGH) of mammalian cell origin. Two hundred and twenty-five patients were previously untreated (naive patients), and 79 were transferred from pituitary hGH after interruption of therapy for at least 6 months (transfer patients). Two treatment protocols, differing in both dose and frequency of injections, were used: (1) a dose of 0.6 IU/kg body weight per week was administered in 3 s.c. injections to 203 patients (178 naive, 25 transfer; group 1); and (2) a dose of 0.45 IU/kg body weight per week was administered in 7 s.c. injections to 101 patients (47 naive, 54 transfer; group 2). After 1 and 2 years of treatment, 143 and 109 naive, and 51 and 46 transfer patients, respectively, were still prepubertal, and their data were analyzed for efficacy. During the 1 st year of treatment, both naive and transfer patients on daily injections (group 2) demonstrated better growth than those on 3 injections per week (group 1), with height velocities (HVs) of 10.6 ± 2.7 cm/year (group 2) versus 8.6 ± 2.0 cm/year (group 1) for naive patients (p < 0.001), and 9.9 ± 1.9 cm/year (group 2) versus 7.2 ± 2.7 cm/year (group 1) for transfer patients (p < 0.001). The corresponding changes in height standard deviation score (ΔH SDS) for chronological age (CA) were + 1.3 ± 0.6 (group 2)versus + 0.8 ± 0.5 (group 1) for naive patients (p < 0.01), and+ 1.1 ± 0.3 (group 2) versus + 0.6 ± 0.4 (group 1) for transfer patients (p < 0.001). For the 2nd treatment year, statistically significant between-group differences in HV and ΔH SDS-CA were seen only in transfer patients, with HVs of 6.8 ± 1.2 (group 2) versus 5.0 ± 1.6 cm/year (group 1) (p < 0.001) corresponding with ΔH SDS of+0.6 ± 0.3 versus +0.2 ± 0.3 (p < 0.001). In naive patients, the mean HV and the corresponding ΔH SDS-CA during the 2nd year were similar in both groups, with an HV of 7.1 ± 1.2 cm/year (group 2) versus 6.6 ± 1.4 cm/year (group 1), and ΔH SDS-CA of+ 0.44 ± 0.29 versus +0.41 ± 0.30, respectively. RhGH treatment was very well tolerated and only 7 patients (2 %) developed anti-hGH antibodies of low affinity and binding capacity persisting longer than 3 months. Thus, authentic rhGH produced in mammalian cells is both efficacious and safe in the treatment of G

ISSN:1663-2818    

DOI:10.1159/000182375

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

91 girls with Turner syndrome (TS) with a mean chronological age (CA) and bone age (BA) of 10.3 ± 2.3 and 8.9 ± 1.9 years, respectively, were randomly assigned to subcutaneous treatment with recombinant human growth hormone (rhGH) alone (n = 47), 2.6 IU/m2 body surface area daily or combination treatment (n = 44) with the same dose of rhGH and oxandrolone 0.1 mg/kg body weight orally, for the first 12 months of this study. During the 1 st year of therapy, there was a striking increase in height velocity (HV) in both groups, from 4.0 ± 0.8 to 6.3 ± 1.3 cm/year [HV standard (standards of untreated Turner patients) deviation score (SDS) for CA from 0.0 ± 0.7 to 2.9 ± 1.3] in the rhGH group and from 4.2 ± 1.2 to 8.5 ± 1.7 cm/year (HV SDS-CA from +0.3 ± 1.0 to+5.6 ± 1.6) in the combination group. The difference between the groups was statistically significant (p < 0.01). During the 2nd year of treatment, the rhGH dose was increased to 3.4 IU/m2 daily for the rhGH-alone group, whereas in the combination treatment group the oxandrolone dose was reduced to 0.05 mg/kg daily. HV was maintained at significantly higher levels than those prior to treatment, at 5.3 ± 1.1 cm/year (HV SDS-CA:+2.1 ± 1.3) and 6.2 ± 1.5 cm/year (HV SDS-CA:+3.6 ± 1.4) in the rhGH-alone and the combination group, respectively (p < 0.001). After 2 years of treatment, the mean predictable adult height had increased by +3.6 ± 2.4 cm in the rhGH-alone group and by +5.3 ± 3.6 cm in the combination group. Both treatment regimens were very well tolerated although clitoral enlargement was seen in 15 of the 44 girls of the combination group who had been treated with 0.1 mg oxandrolone daily for the 1 st year. Impaired glucose tolerance was infrequently seen in girls of either group and the higher oxandrolone dose of the 1st year affected serum lipoprotein levels. Our data suggest that rhGH may improve adult height in girls with TS. This beneficial effect may be further increased by the addition of a low dose of oxandrolone (

ISSN:1663-2818    

DOI:10.1159/000182377

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The development of anti-human growth hormone (anti-hGH) and anti-host-cell protein antibodies to recombinant hGH (rhGH) of mammalian cell origin was determined in 395 children (304 GH deficiency; 91 Turner syndrome) undergoing long-term treatment (up to 54 months) for growth disorders. In all patients, blood samples were obtained prior to and every 2-3 months during treatment, and analyzed at a central laboratory for anti-hGH antibodies by RIA and antibodies to host-cell antigens by ELISA. During the first 24 months of treatment, 9 (3%) of the 304 patients with GH deficiency developed antibodies to rhGH for longer than 3 months. However, persistent antibodies were seen in only 2 patients, both of whom had proven hGH-N gene defects. In the remaining 7 (2%) anti-rhGH-antibody-positive patients, antibody concentrations showed a tendency to increase for 3-12 months, irrespective of the time of onset of measurable concentrations, and declined thereafter. In these patients, binding capacities were between 0.01 and 0.1 mg/l, and binding affinities were between 7 × 108 and 8 × 1091/mol. Height velocity was unaffected in these children. None of the 91 patients with Turner syndrome developed persistent anti-hGH antibodies. Further, no child developed antibodies to host-cell antigens during treatment with rhGH of mammalian cell origi

ISSN:1663-2818    

DOI:10.1159/000182380

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000182382

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000182370

出版商:S. Karger AG    

年代:1992

数据来源: Karger