Pharmacokinetics of single and repeat doses of icatibant

PURPOSE: Icatibant is a bradykinin-2 receptor antagonist approved to treat acute hereditary angioedema attacks in adults. To-date, no thorough investigation of the clinical pharmacokinetic (PK) parameters of icatibant and its primary metabolites has been reported. Here we present the PK results of two phase I clinical studies of icatibant in healthy human volunteers.

METHODS: Single- and multiple-dose plasma pharmacokinetics of icatibant were characterized in healthy volunteers. Icatibant concentration-time profiles and PK parameters were derived after a single 30- or 90-mg dose or three 30-mg doses given at 6-hour intervals.

RESULTS: Maximal plasma concentrations for the 30-mg (979+/-262ng/mL) and 90-mg doses (2,719+/-666ng/mL) were achieved at <1hour postdose. The total plasma icatibant exposure for the 30- and 90-mg doses was 2,191+/-565 and 6,736+/-1,, respectively, with elimination half-life values of 1.48+/-0.35 and 2.00+/-0.57hours, respectively.

CONCLUSIONS: Single 30- and 90-mg subcutaneous administration of icatibant exhibited dose-proportional PK with no appreciable accumulation upon repeated 30-mg doses administered at 6-hour intervals.
Copyright © 2014, The American College of Clinical Pharmacology.

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