PHARMACOKINETICS AND BIOLOGICAL ACTIONS OF SUBCUTANEOUSLY ADMINISTERED HUMAN BRAIN NATRIURETIC PEPTIDE

Human brain natriuretic peptide (hBNP) has demonstrated favorable hemo dynamic effects in patients with congestive heart failure; however, th e peptidic nature of this compound has focused clinical testing on pro tocols involving intravenous delivery. We have studied subcutaneous de livery as an alternative method of administering hBNP. Administration of 30 mu g/kg hBNP by either subcutaneous or intravenous delivery prot ocols resulted in significant hBNP-immunoreactive material in the plas ma with area under the plasma concentration-time curve values of 310 /- 20 nmolxmins/liter and 137 +/- 47 nmolxmins/ liter, respectively. P lasma cyclic GMP, a surrogate marker of activation of the biological r eceptor for hBNP, was elevated for a longer period of time following s ubcutaneous delivery compared with intravenous delivery. Subcutaneous delivery of 30 mu g/kg hBNP resulted in natriuresis, diuresis and redu ced systolic blood pressure in anesthetized normotensive rabbits, effe cts similar in magnitude yet prolonged in duration compared with those elicited by the same dose of hBNP delivered intravenously. Systolic b lood pressure following hBNP treatment remained below base-line values for 50 and 150 min following intravenous and subcutaneous delivery pr otocols, respectively. These results suggests that subcutaneous delive ry of hBNP may be a viable therapeutic alternative to intravenous mode s of delivery.