Vol. 277, Issue 4, E579-E584, October 1999
Pharmacokinetics of insulin-like growth factor I in
hypopituitarism: correlation with binding proteins
Nelly
Mauras1,
Valerie
Quarmby2, and
Duane C.
Bloedow2
1 Nemours Children's Clinic,
Jacksonville, Florida 32207; and
2 Genentech, South San
Francisco, California 94080
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 µg/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
(Cmax) and time of
Cmax
(Tmax) were observed. Compared with normal individuals studied similarly (using 80 µg/kg), GHD subjects showed a normal absorption half-life, a faster
elimination half-life, lower Cmax,
yet normal Tmax
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.
growth hormone deficiency; insulin-like growth factor binding
protein; acid labile subunit; growth hormone
