title: Pharmacokinetics of single and repeat doses of icatibant.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Leach
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Spencer
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Maryann
authors.initials: M
authors.lastname: Mascelli
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: McCauley
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001920:Bradykinin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D065094:Bradykinin B2 Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065094:Bradykinin B2 Receptor Antagonists; C065679:icatibant; D001920:Bradykinin
keywords: angioedema; biopharmaceutics; clinical research; clinical trials; drug information; drug metabolism; icatibant; pharmacokinetics