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Pharmacokinetics of recombinant human insulin‐like growth factor I given subcutaneously to healthy volunteers and to patients with growth hormone receptor deficiency
Author(s) -
Grahnén A,
Kastrup K,
Heinrich U,
Gourmelen M,
Preece MA,
Vaccarello MA,
GuevaraAguirre J,
Rosenfeld RG,
Sietnieks A
Publication year - 1993
Publication title -
acta pædiatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/j.1651-2227.1993.tb12918.x
Subject(s) - medicine , pharmacokinetics , volume of distribution , endocrinology , bioavailability , subcutaneous injection , insulin like growth factor , half life , distribution (mathematics) , microgram , hormone , insulin , trough level , growth factor , receptor , pharmacology , transplantation , biology , mathematical analysis , biochemistry , mathematics , in vitro , tacrolimus
The pharmacokinetics of recombinant human insulin‐like growth factor I (rhIGF‐I) were studied in healthy volunteers and in patients with growth hormone receptor deficiency (GHRD; Laron syndrome). Following single subcutaneous injections of rhIGF‐I, 40 and 80 μgkg, to healthy volunteers, the peptide was absorbed slowly, with a maximum concentration reached after about 7 hours. Following daily multiple subcutaneous injections of rhIGF‐I, 40 μg/kg, trough concentrations of IGF‐I were increased by 277 ± 50 μg/l (mean ± SD) from baseline. IGF‐I was thus characterized as a low‐clearance peptide, with a clearance and half‐life estimated at about 0.20 ml/minute/kg and 20 hours, respectively, in healthy volunteers. The volume of distribution was low, about 0.20–0.36 litres/kg, the bioavailability of subcutaneously administered rhIGF‐I was 100%, and the rate of production of IGF‐I was estimated to be about 50 μg/kg/day (3.5 mg/day). Patients with GHRD had low baseline IGF‐I concentrations (30–50 μ g/ l) and a much more rapid turnover of IGF‐I compared with that in healthy volunteers. The clearance and half‐life of IGF‐I were estimated to be about 0.60 ml/minute/kg and 6 hours, respectively. The volume of distribution was about the same as in healthy subjects. Due to the rapid turnover of IGF‐I, trough IGF‐I concentrations were increased to just above baseline during subcutaneous injections of 40 μg/kg once daily for 7 days. The maximum increase in IGF‐I levels was 111 ± 12 μg/l and 150 ± 3 μg/l following daily subcutaneous injections of 40 × 1 and 40 × 2 μg/kg for 7 days, respectively.