BIOAVAILABILITY AND BIOACTIVITY OF INTRAVENOUS VS SUBCUTANEOUS INFUSION OF GROWTH-HORMONE IN GH-DEFICIENT PATIENTS

OBJECTIVE The bioavailability of GH immunoreactive serum concentration s is reduced following subcutaneous (s.c.) as compared with intravenou s (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. DESIGN AND MEASUREMENTS In a cro ss-over design 10 GH-deficient patients were randomized to receive GH (0.03 mu g (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 w as discontinued for 5 days, Serum profiles of GH, IGF-I, IGF-II, IGF b inding protein 3 (IGFBP-3), insulin, glucose and non-esterified fatty acids (NEFA) were recorded during the studies, Serum GH was measured b y a polyclonal radio-immunoassay (RIA) and by a double monoclonal immu nofluorimetric assay (DELFIA), RESULTS Higher mean integrated values ( AUG) 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 q ualitatively similar results, but higher mean GH concentrations were m easured 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 (mu g/ 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 s hort-term GH treatment and by the route of GH administration. Serum IG FBP-3 levels increased in response to GH administration (P < 0.001), i rrespective of route (P = 0.76), The IGF-II IGFBP-3 molar ratio increa sed significantly following GH administration (P < 0.001), and a highe r 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 respirato ry exchange ratio (P = 0.09) were observed on the two occasions, CONCL USIONS A reduced bioavailability of s.c. as compared with i.v. adminis tered GH has been recorded with two independent GH assays, and this wa s also accompanied by a significant, albeit modest, reduction in biolo gical activity.