Vol. 287, Issue 1, 67-71, October 1998

Pharmacokinetics and Biological Actions of Subcutaneously Administered Human Brain Natriuretic Peptide

L. Edward Clemens, Ramona G. Almirez, Karine A. Baudouin, Ronald P. Mischak, Elliott B. Grossbard and Andrew A. Protter

Scios Incorporated, Mountain View, California

Human brain natriuretic peptide (hBNP) has demonstrated favorable hemodynamic effects in patients with congestive heart failure; however, the peptidic nature of this compound has focused clinical testing on protocols involving intravenous delivery. We have studied subcutaneous delivery as an alternative method of administering hBNP. Administration of 30 µg/kg hBNP by either subcutaneous or intravenous delivery protocols resulted in significant hBNP-immunoreactive material in the plasma with area under the plasma concentration-time curve values of 310 ± 20 nmol×mins/liter and 187 ± 47 nmol×mins/liter, respectively. Plasma cyclic GMP, a surrogate marker of activation of the biological receptor for hBNP, was elevated for a longer period of time following subcutaneous delivery compared with intravenous delivery. Subcutaneous delivery of 30 µg/kg hBNP resulted in natriuresis, diuresis and reduced systolic blood pressure in anesthetized normotensive rabbits, effects similar in magnitude yet prolonged in duration compared with those elicited by the same dose of hBNP delivered intravenously. Systolic blood pressure following hBNP treatment remained below base-line values for 50 and 150 min following intravenous and subcutaneous delivery protocols, respectively. These results suggests that subcutaneous delivery of hBNP may be a viable therapeutic alternative to intravenous modes of delivery.