title: Single-dose pharmacokinetics and safety of azilsartan medoxomil in children and adolescents with hypertension as compared to healthy adults.
abstract: OBJECTIVE
  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 AUC0-∞, 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).
authors.affiliation: Department of Paediatric Nephrology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK. Nicholas.Webb@cmft.nhs.uk.|Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK. Nicholas.Webb@cmft.nhs.uk.
authors.forename: Nicholas J A
authors.initials: NJ
authors.lastname: Webb
authors.affiliation: University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wells
authors.affiliation: Takeda Development Center Americas, Inc., Deerfield, IL, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Tsai
authors.affiliation: Takeda Development Center Americas, Inc., Deerfield, IL, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Takeda Development Centre Europe, Ltd, London, UK.
authors.forename: Attila
authors.initials: A
authors.lastname: Juhasz
authors.affiliation: Takeda Development Center Americas, Inc., Deerfield, IL, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dudkowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D010069:Oxadiazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D010069:Oxadiazoles; C557413:azilsartan medoxomil
keywords: Angiotensin receptor blocker; Azilsartan medoxomil; Dosing; Pediatric; Pharmacokinetics