Development, production and pharmacodynamics of human growth hormone.

With the advent of recombinant DNA technology, it is possible to produce biosynthetic human growth hormone (B-hGH). Novo Nordisk A/S has developed a method for manufacturing B-hGH which is identical to the 22K fraction of pituitary human growth hormone (P-hGH), using a nonpathogenic strain of Escherichia coli as host. B-hGH has been investigated extensively in physical, chemical and biological studies and found to be identical to P-hGH. Pharmacological studies have revealed that B-hGH possesses the same pharmacokinetic and short-term metabolic profiles as P-hGH. Long term clinical studies have shown that B-hGH induces a significant increase in height velocity in children with growth hormone deficiency (GHD) and is characterized by a low antigenicity.

Growth hormone therapy with a new delivery system.

Until recently the general regimen for treatment of growth hormone deficient (GHD) children consisted of 2 to 3 intramuscular (i.m.) injections per week using conventional syringes and vials. However, studies within the last 5-10 year have shown that by dividing the same total weekly dosage into daily subcutaneous (s.c.) injections it is possible to achieve a significantly increased growth rate. To make it more feasible for the patients and the parents to cope with this increased number of injections, an injection pen system (Nordiject) for administration of B-hGH has been developed. The Nordiject pen has been investigated both with respect to patient acceptance and bioavailability of the B-hGH (Norditropin) injected with the device. Twenty-seven children with growth retardation were included in a study. The patients had no problems with the handling of the pen and approximately 2/3 of them experienced less injection pain with the pen compared to the syringe. Those patients who had previously been using conventional syringes strongly preferred the pen, and all wished to continue using the device. Fourteen adult GHD patients were included in a randomized cross-over study for investigation of bioavailability. Two separate s.c. injections of 4 IU of B-hGH (Norditropin) each were administered in random order by means of either syringe (4IU/ml) or injection pen (Nordiject) (12 IU/ml). On the basis of this study it was concluded that the bioavailability of B-hGH, measured as AUC, Cmax, and tmax, is equal following injection with the pen to that of injection by syringe.