Pharmacokinetics of insulin-like growth factor I in hypopituitarism: correlation with binding proteins.
We investigated the pharmacokinetics of recombinant human insulin-like growth factor I (rhIGF-I) in growth hormone deficiency (GHD). Nine GHD adults [age 25 +/- 3 (SE) yr] received rhIGF-I (60 microgram/kg sc) twice, 10 h apart, and blood was sampled over 24 h. IGF-I and free IGF-I concentrations increased, whereas IGF binding protein 3 (IGFBP-3) and acid labile subunit (ALS) were unchanged during treatment. There was no correlation between absorption or terminal half-life of IGF-I and IGFBP-3 or ALS, but negative correlations with IGF-I clearance (CL/F) and volume of distribution (V/F). Positive correlations between both IGFBP-3 and ALS and IGF-I maximal concentration (C(max)) and time of C(max) (T(max)) were observed. Compared with normal individuals studied similarly (using 80 microgram/kg), GHD subjects showed a normal absorption half-life, a faster elimination half-life, lower C(max), yet normal T(max) and V/F. In conclusion, GHD is associated with normal absorption and distribution of IGF-I yet faster elimination kinetics. Additionally, IGFBP-3 and ALS concentrations modulate the peak concentrations of IGF-I achieved and correlate reciprocally with its V/F and CL/F, underscoring the critical importance of binding proteins in modulating the bioavailability of IGF-I in vivo in humans.
Mauras
N
N
Nemours Children's Clinic, Jacksonville, Florida 32207, USA.
Quarmby
V
V
Bloedow
D C
DC
D000042:Absorption; D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood; D013006:Growth Hormone / Q000172:deficiency*; D006207:Half-Life; D019382:Human Growth Hormone / Q000032:analysis / Q000493:pharmacokinetics*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D009994:Osmolar Concentration; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics
D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; C075944:insulin-like growth factor binding protein, acid labile subunit; D019382:Human Growth Hormone; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone