Pharmacokinetics and metabolic effects of growth hormone injected subcutaneously in growth hormone deficient patients: thigh versus abdomen.

OBJECTIVE

The absorption of insulin following subcutaneous (s.c.) injection is faster in the abdomen than the thigh. We therefore studied the effect of changing the site of injection on the absorption and metabolic effects of human growth hormone.

DESIGN AND MEASUREMENTS

In a cross-over study human GH (Norditropin) was injected s.c. in the thigh or abdomen in random order. Ultrasonography of the thigh and abdomen was performed in order to evaluate the thickness of the s.c. tissue. After each treatment period (4 weeks), serum profiles of GH, IGF-I, IGF binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), glucose, insulin, non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate, alanine, lactate and glucagon were measured for 37 hours after GH injection (3 IU/m2 at 1900 hour).

PATIENTS

Nine GH deficient patients (five males, four females).

RESULTS

The mean (+/- SEM) thickness of the s.c. tissue (mm) was higher on the abdominal site (9.35 +/- 1.38 (thigh), and 22.61 +/- 2.19 (abdomen), P < 0.001). Mean (+/- SEM) integrated levels (area under the curves (AUC) divided by time) of GH (mU/l) were identical: 5.54 +/- 0.70 (thigh) versus 5.48 +/- 0.64 (abdomen) (P = 0.91). AUC (mU/l) for the initial 6 hours were, however, significantly different (14.10 +/- 3.76 (thigh) and 19.02 +/- 3.18 (abdomen), P = 0.02). Maximal serum concentration (Cmax) (mU/l) 23.18 +/- 3.86 (thigh) and 29.66 +/- 4.78 (abdomen) (P = 0.19) was achieved faster (Tmax) following injection in the abdomen. Tmax (hours) was 5.89 +/- 0.41 (thigh) and 4.26 +/- 0.49 (abdomen) (P < 0.002). Mean IGF-I levels (microgram/l) were unaffected by GH injection sites (355 +/- 60 (thigh) and 365 +/- 63 (abdomen), P = 0.61). Mean IGFBP-3 levels (microgram/l) were significantly different (2100 +/- 143 (thigh), and 2350 +/- 176 (abdomen), P = 0.05). Mean levels of IGFBP-1, insulin, glucose, lipid intermediates, metabolites and glucagon were not significantly different.

CONCLUSIONS

Human GH was absorbed faster when injected s.c. in the abdomen as compared with the thigh, despite the thicker s.c. tissue on the abdomen. Apart from higher IGFBP-3 levels after s.c. injections in the abdomen, similar metabolic effects of GH were obtained with the two injection sites.