Bioavailability and bioactivity of intravenous vs subcutaneous infusion of growth hormone in GH-deficient patients.
OBJECTIVE
The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the present study was to evaluate the short-term metabolic effects of GH following i.v. and s.c. delivery.


METHODS
In a cross-over design 10 GH-deficient patients were randomized to receive GH (0.03 microgram (0.1 mU/kg/min) as a continuous i.v. or s.c. infusion for 39 hours on two different occasions. Preceding each study GH therapy was discontinued for 5 days. Serum profiles of GH, IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3), insulin, glucose and non-esterified fatty acids (NEFA) were recorded during the studies. Serum GH was measured by a polyclonal radio-immunoassay (RIA) and by a double monoclonal immunofluorimetric assay (DELFIA).


RESULTS
Higher mean integrated values (AUC) of serum GH (mU/l) were obtained with i.v. GH delivery [47.4 +/- 5.1 (i.v.), 33.3 +/- 3.0 (s.c.), P < 0.05]. The two GH assays showed qualitatively similar results, but higher mean GH concentrations were measured by RIA following both s.c. (P < 0.001) and i.v. infusion (P < 0.001). Serum IGF-I levels displayed different patterns following i.v. and s.c. GH infusion (P < 0.05 by ANOVA) and mean IGF-I levels (micrograms/l) were lower following s.c. GH infusion [159.5 +/- 21.8 (s.c.), 185.2 +/- 27.7 (i.v.), P = 0.002]. Serum IGF-II levels were unaffected by short-term GH treatment and by the route of GH administration. Serum IGFBP-3 levels increased in response to GH administration (P < 0.001), irrespective of route (P = 0.76). The IGF-I/IGFBP-3 molar ratio increased significantly following GH administration (P < 0.001), and a higher ratio was obtained following i.v. infusion (P < 0.005). Subcutaneous GH infusion resulted in significantly lower mean levels of serum NEFA (P < 0.02), whereas similar mean levels of serum insulin (P = 0.54), blood glucose (P = 0.24), energy expenditure (P = 0.13), and respiratory exchange ratio (P = 0.09) were observed on the two occasions.


CONCLUSIONS
A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant, albeit modest, reduction in biological activity.
Laursen
T
T
Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Denmark.
Møller
J
J
Jørgensen
J O
JO
Orskov
H
H
Christiansen
J S
JS
D000328:Adult; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism; D013006:Growth Hormone / Q000172:deficiency* / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone