Tags

Type your tag names separated by a space and hit enter

Pharmacokinetic studies of recombinant human insulin-like growth factor I (rhIGF-I)/rhIGF-binding protein-3 complex administered to patients with growth hormone insensitivity syndrome.
J Clin Endocrinol Metab. 2006 Apr; 91(4):1246-53.JC

Abstract

CONTEXT

GH insensitivity syndrome (GHIS), Laron syndrome, is characterized by severe short stature, high serum GH levels, and very low serum IGF-I and IGF-binding protein-3 (IGFBP-3) levels associated with a genetic defect of the GH receptor. Recombinant human (rh) IGF-I treatment at doses of 80-120 microg/kg given sc twice daily is effective in promoting growth in these patients. We have investigated a newly developed drug, rhIGF-I/rhIGFBP-3, a 1:1 molar complex of rhIGF-I and rhIGFBP-3.

OBJECTIVES

The objectives of the study were to determine IGF-I pharmacokinetics after the administration of rhIGF-I/rhIGFBP-3 in adolescents with GHIS and to evaluate its safety and tolerability.

DESIGN

This was an open-label clinical study.

SETTING

The study was conducted in a general pediatric ward of a university teaching hospital.

PARTICIPANTS

Four patients (one female and three males; mean age, 14.9 yr; mean height sd score, -4.9) with confirmed molecular diagnosis of GHIS agreed to participate in the study.

INTERVENTION

rhIGF-I/rhIGFBP-3 was administered in a single sc injection at 0.5 and 1.0 mg/kg.dose (equivalent to 100 and 200 microg/kg rhIGF-I) after breakfast with a 2-d interval between doses.

RESULTS

IGF-I levels reached a maximum between 19 +/- 8.3 and 15 +/- 6.2 h for the low and high doses, respectively. The circulating IGF-I levels obtained with the low and high doses were similar, although a discrete dose-dependent increase in circulating IGF-I levels was observed. The IGF-I half-life in four subjects after a dose of 0.5 mg/kg rhIGF-I/rhIGFBP-3 was estimated to be 21+/- 4 h. There were no acute adverse events reported, and all blood glucose measurements were normal.

CONCLUSION

These data demonstrated that the rhIGF-I/rhIGFBP-3 complex was effective in increasing levels of circulating total and free IGF-I into the normal range for a 24-h period after a single sc administration in patients with GHIS, and that administration of rhIGF-I/rhIGFBP-3 was safe and well tolerated.

Authors+Show Affiliations

Department of Endocrinology, William Harvey Research Institute, John Vane Science Building, First Floor, Charterhouse Square, London EC1M 6BQ, United Kingdom. c.camacho-hubner@qmul.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16403822

Citation

Camacho-Hübner, Cecilia, et al. "Pharmacokinetic Studies of Recombinant Human Insulin-like Growth Factor I (rhIGF-I)/rhIGF-binding Protein-3 Complex Administered to Patients With Growth Hormone Insensitivity Syndrome." The Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 4, 2006, pp. 1246-53.
Camacho-Hübner C, Rose S, Preece MA, et al. Pharmacokinetic studies of recombinant human insulin-like growth factor I (rhIGF-I)/rhIGF-binding protein-3 complex administered to patients with growth hormone insensitivity syndrome. J Clin Endocrinol Metab. 2006;91(4):1246-53.
Camacho-Hübner, C., Rose, S., Preece, M. A., Sleevi, M., Storr, H. L., Miraki-Moud, F., Minuto, F., Frystyk, J., Rogol, A., Allan, G., Sommer, A., & Savage, M. O. (2006). Pharmacokinetic studies of recombinant human insulin-like growth factor I (rhIGF-I)/rhIGF-binding protein-3 complex administered to patients with growth hormone insensitivity syndrome. The Journal of Clinical Endocrinology and Metabolism, 91(4), 1246-53.
Camacho-Hübner C, et al. Pharmacokinetic Studies of Recombinant Human Insulin-like Growth Factor I (rhIGF-I)/rhIGF-binding Protein-3 Complex Administered to Patients With Growth Hormone Insensitivity Syndrome. J Clin Endocrinol Metab. 2006;91(4):1246-53. PubMed PMID: 16403822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic studies of recombinant human insulin-like growth factor I (rhIGF-I)/rhIGF-binding protein-3 complex administered to patients with growth hormone insensitivity syndrome. AU - Camacho-Hübner,Cecilia, AU - Rose,Stephen, AU - Preece,Michael A, AU - Sleevi,Mark, AU - Storr,Helen L, AU - Miraki-Moud,Farideh, AU - Minuto,Francesco, AU - Frystyk,Jan, AU - Rogol,Alan, AU - Allan,Geoffrey, AU - Sommer,Andreas, AU - Savage,Martin O, Y1 - 2006/01/10/ PY - 2006/1/13/pubmed PY - 2006/5/2/medline PY - 2006/1/13/entrez SP - 1246 EP - 53 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 91 IS - 4 N2 - CONTEXT: GH insensitivity syndrome (GHIS), Laron syndrome, is characterized by severe short stature, high serum GH levels, and very low serum IGF-I and IGF-binding protein-3 (IGFBP-3) levels associated with a genetic defect of the GH receptor. Recombinant human (rh) IGF-I treatment at doses of 80-120 microg/kg given sc twice daily is effective in promoting growth in these patients. We have investigated a newly developed drug, rhIGF-I/rhIGFBP-3, a 1:1 molar complex of rhIGF-I and rhIGFBP-3. OBJECTIVES: The objectives of the study were to determine IGF-I pharmacokinetics after the administration of rhIGF-I/rhIGFBP-3 in adolescents with GHIS and to evaluate its safety and tolerability. DESIGN: This was an open-label clinical study. SETTING: The study was conducted in a general pediatric ward of a university teaching hospital. PARTICIPANTS: Four patients (one female and three males; mean age, 14.9 yr; mean height sd score, -4.9) with confirmed molecular diagnosis of GHIS agreed to participate in the study. INTERVENTION: rhIGF-I/rhIGFBP-3 was administered in a single sc injection at 0.5 and 1.0 mg/kg.dose (equivalent to 100 and 200 microg/kg rhIGF-I) after breakfast with a 2-d interval between doses. RESULTS: IGF-I levels reached a maximum between 19 +/- 8.3 and 15 +/- 6.2 h for the low and high doses, respectively. The circulating IGF-I levels obtained with the low and high doses were similar, although a discrete dose-dependent increase in circulating IGF-I levels was observed. The IGF-I half-life in four subjects after a dose of 0.5 mg/kg rhIGF-I/rhIGFBP-3 was estimated to be 21+/- 4 h. There were no acute adverse events reported, and all blood glucose measurements were normal. CONCLUSION: These data demonstrated that the rhIGF-I/rhIGFBP-3 complex was effective in increasing levels of circulating total and free IGF-I into the normal range for a 24-h period after a single sc administration in patients with GHIS, and that administration of rhIGF-I/rhIGFBP-3 was safe and well tolerated. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/16403822/Pharmacokinetic_studies_of_recombinant_human_insulin_like_growth_factor_I__rhIGF_I_/rhIGF_binding_protein_3_complex_administered_to_patients_with_growth_hormone_insensitivity_syndrome_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2005-1017 DB - PRIME DP - Unbound Medicine ER -