Single-dose pharmacokinetics and safety of azilsartan medoxomil 5 in children and adolescents with hypertension as compared 6 to healthy adults

PURPOSE: This open-label, multicenter, single-dose study characterized the pharmacokinetics and short-term safety of azilsartan medoxomil (AZL-M) in hypertensive pediatric subjects (12–16 years [cohort 1a; n = 9]; 6–11 years [cohort 2; n = 8]; 4–5 years [cohort 3; n = 3]). METHODS: Model-based simulations were performed to guide dosing, especially in 1–5-year olds, who were difficult to enroll. AZL-M was dosed according to body weight (20–60-mg tablet, cohorts 1a and 2; 0.66 mg/kg granule suspension, cohort 3). In cohort 1, gender-matched healthy adults (cohort 1b; n = 9) received AZL-M 80 mg. RESULTS: Exposure to AZL (active moiety of AZL-M), measured by dose-/body weight-normalized C(max) and AUC(0–∞), was ∼15–30 % lower in pediatric subjects versus adults. In simulations, exposure with 0.66 mg/kg AZL-M in pediatric subjects weighing 8–25 kg approximated to AZL-M 40 mg (typical starting dose) in adults. The simulations suggest that 25–50-kg subjects require half the adult dose (10–40 mg), whereas 50–100-kg subjects can use the same dosing as adults. Adverse events were mild in intensity, apart from one moderate event (migraine). CONCLUSIONS: This dosing strategy should be safe in pediatric patients, as AZL exposure would not exceed that seen in adults with the highest approved AZL-M dose (80 mg). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00228-015-1987-8) contains supplementary material, which is available to authorized users