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 ± 262 ng/mL) and 90-mg doses (2,719 ± 666 ng/mL) were achieved at <1 hour postdose. The total plasma icatibant exposure for the 30- and 90-mg doses was 2,191 ± 565 and 6,736 ± 1,230 h · ng/mL, respectively, with elimination half-life values of 1.48 ± 0.35 and 2.00 ± 0.57 hours, 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.