PT  - JOURNAL ARTICLE
AU  - L. Edward Clemens
AU  - Ramona G. Almirez
AU  - Karine A. Baudouin
AU  - Ronald P. Mischak
AU  - Elliott B. Grossbard
AU  - Andrew A. Protter
TI  - Pharmacokinetics and Biological Actions of Subcutaneously Administered Human Brain Natriuretic Peptide
DP  - 1998 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 67--71
VI  - 287
IP  - 1
4099  - http://jpet.aspetjournals.org/content/287/1/67.short
4100  - http://jpet.aspetjournals.org/content/287/1/67.full
SO  - J Pharmacol Exp Ther1998 Oct 01; 287
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics