Prospects for the development of long-acting formulations of human somatropin.

Abstract

In healthy humans, growth hormone (GH) is secreted in distinct pulses with an underlying nyctohemeral pattern. Current forms of somatropin replacement are unable to closely mimic such a release pattern, but are still able to exert the beneficial action of GH. A limited number of short-term studies in rodents and humans suggest that longitudinal growth may be superior when somatropin is given with a pulsatile mode of administration, whereas hepatic insulin-like growth factor-I generation and beneficial changes in body composition appear to be equal or even enhanced with continuous somatropin administration.Recent developments in drug delivery technology have allowed the use of slow-release preparations of somatropin in humans. The most successful technology so far has been the encapsulation of somatropin molecules in poly(D,L-lactic-co-glycolic acid) biodegradable microspheres. Pharmacokinetic and pharmacodynamic data have been published on two such preparations; Nutropin Depot((R)) and hGH-Biosphere((R)). The latter has a superior release profile, but outcomes data from multicenter trials in both children and adults have been presented for the former: catch-up growth was observed in children, although to a lesser degree than historic comparative data obtained with the use of daily somatropin injections and the effects on metabolic derangements in GH-deficient patients appeared similar to those observed with daily injections. Improved sustained-release somatropin preparations will need further study of their long-term efficacy, but, if successful, will be highly attractive in terms of patient compliance and convenience.