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Administration of human recombinant insulin‐like growth factor‐I to patients following major gastrointestinal surgery
Author(s) -
Miell John P.,
Taylor Alastair M.,
Jones Jennifer,
Buchanan Charles R.,
Rennie John,
Sherwood Roy,
Leicester Roger,
Ross Richard J. M.
Publication year - 1992
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1992.tb01486.x
Subject(s) - medicine , endocrinology , placebo , radioimmunoassay , insulin , insulin like growth factor , blood sampling , creatinine , basal (medicine) , pharmacokinetics , growth factor , receptor , alternative medicine , pathology
Summary OBJECTIVE The aim was to study the pharmacokinetic parameters and biological activity of a single dose of human recombinant IGF‐I (rhIGF‐I) administered to patients following major gastrointestinal surgery. DESIGN A double blind placebo controlled externally randomized study of 30 patients; the study commencing 24 hours after major colonic or gastric surgery. MEASUREMENTS After a baseline blood sampling day, IGF‐I (40 μg/kg by single subcutaneous dose, n = 20) or placebo ( n = 10) was administered and serum and urine samples collected over the ensuing 72 hours. Serum IGF‐I, IGF‐II, IGF binding proteins (IGFBP‐1, IGFBP‐3), GH and insulin were measured by radioimmunoassay. Serum IGF bioactivity was assessed using a validated porcine cartilage bioassay. Serum and urinary electrolytes were measured by standard methodology. RESULTS Serum immunoreactive IGF‐I levels peaked at 4hours following injection of IGF‐I (1– 0.9 ± 0.12 U/ml mean ± SEM), remained elevated for 15 hours and returned to basal levels by 24 hours after injection. IGF bioactivity was increased by 57% 6 hours after IGF‐I injection. Mean levels of IGFBP‐1 and IGFBP‐3, IGF‐II and GH were unaffected by IGF‐I administration. Insulin levels were suppressed at 30 minutes following injection of IGF‐I compared with the placebo group (16.9 ± 3.0 mU/l vs 32.3 ± 7.1, P =0.02); thereafter, there were no differences in insulin levels. The mean change in serum creatinine following IGF‐I (‐6.3 ± 3.0 mmol/l) was significantly different from that in the control group (± 7.2 ± 6.2, P = 0.03). Creatinine clearance rose from a mean of 71.6 ± 7.5 ml/ min to 83.2 ± 7.6 ml/min after IGF‐I treatment ( P = 0.02). In the IGF treated patients, cholesterol levels consistently fell (‐0.20 ± 0.05 mmol/l); this was not observed in the placebo group (+ 0.20 ± 0.14, P =0.006). Basal serum potassium levels in the IGF treatment group (4.1 ± 0.1 mmol/l) fell to 3.8 ± 0.1 at 4 hours ( P = 0.002) and 3.6 ± 0.1 at 10 hours ( P = 0.001) returning to a level of 4.0 ± 0.1 ( P = 0.293) at 24 hours after injection. There were no other observed differences in serum or urinary electrolytes or serum free fatty acids and triglycerides. Pharmacokinetic parameters derived from baseline adjusted IGF‐I measurements revealed a slow absorption of the administered dose with a T max of 5.0 ± 0.43 hours and an elimination half‐life of 10.8 ± 1.2 hours. The computed volume of distribution was 0.33 ± 0.05 l/kg and the clearance on average 25 ml/min. CONCLUSIONS A single subcutaneous dose of IGF‐I normalized circulating IGF‐I levels in post‐operative patients, was well tolerated and without side‐effects. IGF bioactivity was increased and associated with a fall in serum cholesterol, potassium and creatinine levels and a rise in creatinine clearance. Further long‐term studies are now required to assess the anabolic effects of rhIGF‐I in this type of patient group.