Pharmacokinetics of insulin-like growth factor-1 in advanced chronic renal failure
| Autor: | John O. Ike, Andrew R. Hoffman, Raymond L. Hintz, Duane C. Bloedow, Neil Gesundheit, Fernando C. Fervenza, Ralph Rabkin, Helen Maidment, Frances Liu |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.medical_treatment Blotting Western law.invention Insulin-like growth factor chemistry.chemical_compound Pharmacokinetics Pregnancy law Internal medicine Humans Medicine Distribution (pharmacology) Insulin-Like Growth Factor I Volume of distribution Creatinine business.industry Blood Proteins Middle Aged Blood proteins Blot Kinetics Endocrinology chemistry Nephrology Recombinant DNA Kidney Failure Chronic Female business hormones hormone substitutes and hormone antagonists Protein Binding |
| Zdroj: | Kidney International. 49:1134-1140 |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.1996.164 |
| Popis: | Pharmacokinetics of insulin-like growth factor-1 in advanced chronic renal failure. Information regarding the impact of chronic renal failure (CRF) on IGF-1 serum clearance is limited. Thus we evaluated the pharmacokinetics of insulin-like growth factor-1 (IGF-1) in six normal adults and six adults with advanced CRF (serum creatinine 7 ± 0.8 mg/dl). All subjects were given 80 µg/kg recombinant human IGF-1 s.c. and blood was sampled over 48 hours. Baseline total serum IGF-1 levels were similar in both groups, but peak levels were elevated significantly in CRF; this was apparently related to the reduced distribution volume in CRF subjects. CRF did not affect the metabolic clearance rate (MCR) of total serum IGF-1. Immunoreactive IGF binding protein-3 (IGFBP-3) levels were greater in CRF. Western immunoblots revealed that the apparent increase in IGFBP-3 was largely due to an increase in immunoreactive fragments. IGFBP-3 protease activity was not increased. Thus IGFBP fragment accumulation likely reflects reduced fragment clearance. Western ligand blots revealed elevated 30 and 34kDa IGFBP levels and IGFBP products in CRF serum. Serum acid labile subunit levels were unchanged in CRF. Peak free IGF-1 levels and the MCR of free IGF-1 did not differ between groups. In both groups the MCR of free IGF-1 exceeded the MCR of total IGF-1 by approximately 30-fold. These data suggest that in CRF patients receiving s.c. IGF-1: (a) total serum IGF-1 levels are increased as a result of elevated circulating IGFBPs that may restrict the distribution of IGF-1 beyond plasma; (b) serum free IGF-1 levels are not altered; and (c) the IGF-1 MCR is unchanged in CRF. Thus, in advanced CRF, apart from a reduction in the total IGF-1 volume of distribution the pharmacokinetics of IGF-1 are largely unaltered. |
| Databáze: | OpenAIRE |
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