Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration

OBJECTIVE: Pharmacokinetic and pharmacodynamic data after recombinant human GH (rhGH) administration in adults are scarce, but necessary to optimize replacement therapy and to detect doping. We examined pharmacokinetics, pharmacodynamics, and 20 kDa GH after injection of rhGH at different doses and routes of administration. DESIGN: Open-label crossover study with single boluses of rhGH. METHODS: Healthy trained subjects (10 males, 10 females) received bolus injections of rhGH on three occasions: 0.033 mg/kg s.c., 0.083 mg/kg s.c., and 0.033 mg/kg i.m. Concentrations of 22 and 20 kDa GH, IGF-I, and IGF-binding proteins (IGFBP)-3 were measured repeatedly before and up to 36 h after injection. RESULTS: Serum GH maximal concentration (Cmax) and area under the time-concentration curve (AUC) were higher after i.m. than s.c. administration of 0.033 mg/kg (Cmax 35.5 and 12.0 microg/l; AUC 196.2 and 123.8). Cmax and AUC were higher in males than in females (P < 0.01) and pharmacodynamic changes were more pronounced. IGFBP-3 concentrations showed no dose dependency. In response to rhGH administration, 20 kDa GH decreased in females and remained suppressed for 14-18 h (low dose) and 30 h (high dose). In males, 20 kDa GH was undetectable at baseline and throughout the study. CONCLUSIONS: After rhGH administration, pharmacokinetic parameters are mainly influenced by route of administration, whereas pharmacodynamic variables and 20 kDa GH concentrations are determined mainly by gender. These differences need to be considered for therapeutic use and for detection of rhGH doping.