Pharmacokinetics of single and repeat doses of icatibant

• Published in: Clinical pharmacology in drug development Vol. 4; no. 2; pp. 105 - 111
• Main Authors: Leach, J. Kevin, Spencer, Kelly, Mascelli, Maryann, McCauley, Thomas G.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2015; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; angioedema; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - blood; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Area Under Curve; biopharmaceutics; Bradykinin - administration & dosage; Bradykinin - adverse effects; Bradykinin - analogs & derivatives; Bradykinin - blood; Bradykinin - pharmacokinetics; Bradykinin B2 Receptor Antagonists - administration & dosage; Bradykinin B2 Receptor Antagonists - adverse effects; Bradykinin B2 Receptor Antagonists - blood; Bradykinin B2 Receptor Antagonists - pharmacokinetics; clinical research; clinical trials; Drug Administration Schedule; drug information; drug metabolism; Female; Half-Life; Healthy Volunteers; Humans; icatibant; Injections, Subcutaneous; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; pharmacokinetics; Young Adult; angioedema; drug information; clinical research; drug metabolism; pharmacokinetics; clinical trials; biopharmaceutics; icatibant
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.138

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.