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Icatibant has no impact on renal function in healthy subjects
Author(s) -
Rousso P.,
Nguyen M.,
Perrin Y.,
Buclin T.,
Décosterd L. A.,
Nussberger J.,
Appenzeller M.,
Jaquet F.,
BrunnerFerber F.,
Rosenkranz B.,
Knolle J.,
Biollaz J.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.215
Subject(s) - icatibant , renal function , medicine , pharmacology , bradykinin , receptor
The role of bradykinin (BK) in renal regulations is still controversial. To elucidate whether Icatibant, a potent BK antagonist on B2 receptors, can interfere with renal function under normal conditions, we performed sinistrin and para‐aminohippurate (PAH) clearances, plasma levels and excretion rate of electrolytes, albumin, urate, endogenous lithium, as well as plasma renin, aldosterone and endothelin in 14 healthy males under Icatibant infusion. Part I (2 panels of 4 subjects) compared single 4h infusions (0.005 to 0.8 mg/kg) in ascending, double‐blind, placebo‐controlled design. Part II tested renal function on the 3rd day of a 72h Icatibant or placebo infusion, in a 2‐way crossover, double blind design. No changes in glomerular filtration rate (sinistrin), renal blood flow (PAH), or in proximal renal tubular function (lithium and urate clearances) were detected. Sodium, potassium and chloride excretions, micro‐albuminuria, urinary volume, and hematocrit remained unchanged. Vital signs (supine and orthostatic blood pressure, heart rate), body weight, and hormone concentrations were also unaltered. The safety and tolerability of Icatibant was excellent. This study had enough power to detect physiologically significant effects but not even trends for changes in renal function could be suspected. In conclusion, these results strongly advocate against a physiological role of BK in the regulation of renal function under normal conditions. Clinical Pharmacology & Therapeutics (2004) 75 , P57–P57; doi: 10.1016/j.clpt.2003.11.215