PHARMACOKINETICS AND SHORT TERM METABOLIC EFFECTS OF PITUITARY AND BIOSYNTHETIC HUMAN GROWTH HORMONE IN GH-DEFICIENT MAN. A DOUBLE-BLIND CROSSOVER STUDY

Abstract

In a double-blind crossover study we compared pituitary and ‘methionine free’ biosynthetic human growth hormone (P-hGH and B-hGH) with respect to pharmacokinetics and short term metabolic effects in 9 hypopituitary children. They treated themselves for 4 weeks with 2 IU subcutaneously (s.c.) daily at 20.00h. After admittance to hospital 2 IU was given intramusculary (i.m.) the first day, and s.c. the second. They then switched over to the alternative preparation. The pharmacokinetics of B- and P-hGH were identical. Comparing i.m. and s.c. absorption, the latter was slower, and resulted in smaller areas under the curves, indicating greater local degradation. Both preparations caused identical increases in somatomedin C, but slightly more sustained after s.c. inj.P-glucose, -glukagon and s-insulin fluctuated within normal range. The glucose profile pointed at a modest anti-insulin effect of hGH when given in the morning. B-lactate, -alanine, -glycerol and -B-OH-butyrate, and s-TG, -cholesterol and -carbamide revealed no abnormalities with either hGH preparation. Finally, no development of anti-GH or E coli polypeptide antibodies was seen. In conclusion, the pharmacokinetics and short term metabolic effects of B-hGH and P-hGH were identical. Furthermore, the advantage of daily s.c. hGH injections in the evening is once more demonstrated.