Pharmacokinetics of Recombinant Human Growth Hormone (rhGH) in Beagles by ELISA

Abstract

Background:: Somatropin is recombinant human growth (GH) used for the treatment of growth failure in children and GH deficiency in adults. At present, rhGH marketed in China is mostly freeze-dried powder injection. As the lyophilization process is unstable, time-consuming and costly, rhGH has been prepared into an aqueous solution for administering directly. Introduction:: In this study, the pharmacokinetics of two dosage forms of rhGH in beagle dogs after single subcutaneous administration was determined by enzyme-linked immunosorbent assay (ELISA). Methods: Twelve healthy beagles (male, 6:female, 6) were used for the pharmacokinetic study and were equally divided into two groups. Subcutaneous injection of 0.2 IU/kg with rhGH in the two formulations. The blood samples were taken from forearms, 0, 0.033, 0.083, 0.25, 0.5, 1, 2, 3, 4, 7, 10, 24 h and collected the beagle plasma on time. The pharmacokinetic parameters of rhGH after subcutaneous (s.c.) injection were determined experimentally on beagles. Primary PK endpoints were area under the serum concentration-time curve (AUC0-t) and maximum serum concentration (Cmax). Serum rhGH level was determined by enzyme-linked immunosorbent assay. Results:: The calibration curves obtained were linear over the concentration range of 25 to 1600 ng/ml for recombinant human growth. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. The analysis samples were stable under different storage conditions and temperature. Conclusions:: The developed ELISA method has been successfully applied to the studies of pharmacokinetic of recombinant human growth hormone in beagles.