DOSE REGIMENS OF HUMAN GROWTH HORMONE: EFFECTS OF CONTINUOUS INFUSION AND OF A GELATIN VEHICLE ON GROWTH IN RATS AND RATE OF ABSORPTION IN RABBITS

Abstract

Different methods for administration of human growth hormone (hGH) have been examined with a view to efficient use of the limited amounts of hGH at present available for clinical use. We found that in hypophysectomized rats (1) hGH administered by continuous subcutaneous infusion induced a greater increase in body weight (referred to throughout as growth) than hGH administered by intermittent (daily) injection and (2) intermittent injections of hGH dissolved in 16% gelatin induced more growth than hGH dissolved in a glycine buffer. It was further found that (1) hGH dissolved in 16% gelatin compared with hGH dissolved in a glycine buffer induced lower maximal levels of immunoreactive plasma hGH and between 7 and 9 h after treatment higher plasma levels when injected subcutaneously in rabbits, (2) 125I-labelled hGH added as a tracer to hGH in gelatin was removed more slowly from subcutaneous injection sites in rabbits than 125I-labelled hGH given with hGH in glycine buffer and (3) changes in the ratio of hGH to gelatin had little effect on the time-course of plasma levels of hGH in the rabbit. Addition of the protease inhibitors aprotinin or 6-aminohexanoic acid, to injection of hGH in gelatin or glycine did not induce any consistent increase in plasma levels of hGH.