Pharmacokinetics of recombinant human insulin-like growth factor I given subcutaneously to healthy volunteers and to patients with growth hormone receptor deficiency.
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 micrograms/kg, 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 micrograms/kg, trough concentrations of IGF-I were increased by 277 +/- 50 micrograms/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 micrograms/kg/day (3.5 mg/day). Patients with GHRD had low baseline IGF-I concentrations (30-50 micrograms/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 micrograms/kg once daily for 7 days. The maximum increase in IGF-I levels was 111 +/- 12 micrograms/l and 150 +/- 3 micrograms/l following daily subcutaneous injections of 40 x 1 and 40 x 2 micrograms/kg for 7 days, respectively.
Grahnén
A
A
Pharmaco Medical Consultants, Uppsala, Sweden.
Kastrup
K
K
Heinrich
U
U
Gourmelen
M
M
Preece
M A
MA
Vaccarello
M A
MA
Guevara-Aguirre
J
J
Rosenfeld
R G
RG
Sietnieks
A
A
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D004392:Dwarfism / Q000151:congenital / Q000378:metabolism; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011986:Receptors, Somatotropin / Q000172:deficiency*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I