Population Pharmacokinetics and Exposure-Response Analyses to Guide Dosing of Icatibant in Pediatric Patients With Hereditary Angioedema.

Population Pharmacokinetics and Exposure-Response Analyses to Guide Dosing of Icatibant in Pediatric Patients With Hereditary Angioedema. J Clin Pharmacol. 2020 Oct 22;: Authors: Wang Y, Jomphe C, Marier JF, Martin P Abstract Elevated bradykinin levels are responsible for the development of clinical symptoms in patients with hereditary angioedema (HAE). Icatibant is a bradykinin type 2 receptor antagonist indicated for the acute treatment of HAE attacks. A population modeling and simulation approach was used to examine sources of variability impacting icatibant pharmacokinetics (PK) and provide guidance on icatibant dosing in pediatric patients with HAE. An exposure-response analysis was performed for the time to onset of symptom relief (TOSR). Data from 141 adults (133 healthy, 8 with HAE) who received subcutaneous icatibant 30 mg and 31 pediatric patients with HAE who received 0.4 mg/kg (capped at 30 mg) were included in the analysis. Icatibant PK was described by a 2-compartment model with linear elimination. Complete absorption of icatibant was expected within 1 hour of dosing. The apparent clearance and central volume of distribution were 15.4 L/h and 20.4 L, respectively. Icatibant PK was mainly dependent on body weight. The mean TOSR was very short (1.38 hours). A flat exposure-response was observed, confirming that the relationship plateaued at the level of exposure observed in pediatric patients. Simulations confirmed that w...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research