Controlled release of human growth hormone following subcutaneous administration in dogs

Recombinant human growth hormone (rhGH) formulated in poloxamer-407 gel was administered subcutaneously in mixed breed dogs. To calculate pharmacokinetic parameters, all dogs were first administered 0.2 mg/kg of rhGH by an intravenous (i.v.) bolus injection. The i.v. dose was completely cleat-ed in 3 h, with an elimination t(1/2)beta of 0.574 h and t(1/2)alpha of 0.068 h. After a wash out period of 7 days, all dogs received 0.7 mg/kg of rhGH subcutaneously as a gel formulation. Blood samples were drawn at frequent intervals for 132 h. Subcutaneous administration of the gel resulted in a peak maxima, 9 h after injection and concentrations of rhGH remained in the therapeutic window for 132 h. As compared to rhGH solutions, rhGH formulated in poloxamer gel resulted in a decrease in the maximum blood concentration and increased the time required to achieve maximum blood concentration. Hence, this approach may be promising for controlled release of rhGH, but needs further investigation to avoid a initial burst effect that was seen and to account for an observed loss of a portion of the administered dose. (C) 1997 Elsevier Science B.V.