title: Pharmacokinetics of olmesartan medoxomil in pediatric patients with hypertension.
abstract: BACKGROUND
  The prevalence and importance of hypertension in younger patients is becoming increasingly recognized; however, only a limited number of clinical trials have been conducted in the pediatric population.
  
  
  OBJECTIVE
  The aim of this study was to characterize the pharmacokinetics and short-term safety of olmesartan medoxomil in children and adolescents with hypertension.
  
  
  METHODS
  An open-label, multicenter, single-dose study was conducted in children and adolescents aged 12 months-16 years who were receiving treatment for hypertension or, if not currently treated for hypertension, had either a systolic blood pressure (SBP) or diastolic blood pressure (DBP).≥95th percentile, or SBP or DBP ≥90th percentile if diabetic or with a family history of hypertension. Patients were stratified by age: 12-23 months (Group 1; none enrolled), 2-5 years (Group 2; n = 4), 6-12 years (Group 3; n = 10), and 13-16 years (Group 4; n = 10). All patients received a single oral dose of olmesartan medoxomil based on the individual's age and bodyweight. Patients aged <6 years received an oral suspension of olmesartan medoxomil at a dose of 0.3 mg/kg of bodyweight (not to exceed 20 mg), those aged ≥6 years who weighed ≥35 kg received olmesartan medoxomil 40 mg tablets, and those who weighed <35 kg received olmesartan medoxomil 20 mg tablets.
  
  
  RESULTS
  In Groups 2, 3, and 4, the weight-adjusted apparent total body clearance (CL/F) of olmesartan medoxomil was 0.100 ± 0.034, 0.062 ± 0.020, and 0.072 ± 0.022 L/h/kg, respectively, and the weight-adjusted apparent volume of distribution (Vd/F) was 0.32 ± 0.16, 0.33 ± 0.14, and 0.49 ± 0.23 L/kg, respectively. CL/F and Vd/F in Groups 3 and 4 were not significantly different. Statistical comparisons between Groups 3 or 4 and Group 2 were not performed due to the small sample size of Group 2 (n = 4). Plasma elimination half-life and time to maximum plasma concentration were similar across the three groups. In Groups 3 and 4, considerable interindividual variability was seen in maximum plasma concentration (C(max)), area under the curve (AUC) from time zero to the last measurable concentration, and apparent clearance, with AUC and C(max) approximately 30% greater in Group 3. Four of 24 (16.7%) patients experienced treatment-emergent adverse events that were all mild in severity and considered not drug-related. No deaths, serious adverse events, or discontinuations due to adverse events occurred in the study.
  
  
  CONCLUSIONS
  Olmesartan medoxomil was well tolerated and demonstrated a pharmacokinetic profile in pediatric patients similar to that of adults when adjusted for body size.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00151814
authors.affiliation: Arkansas Childrens Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wells
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Blowey
authors.forename: Janice E
authors.initials: JE
authors.lastname: Sullivan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Blumer
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Sherbotie
authors.forename: Saeheum
authors.initials: S
authors.lastname: Song
authors.forename: Shashank
authors.initials: S
authors.lastname: Rohatagi
authors.forename: Reinilde
authors.initials: R
authors.lastname: Heyrman
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Salazar
mesh_terms: D000293:Adolescent; D057912:Angiotensin II Type 2 Receptor Blockers / Q000009:adverse effects / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D007223:Infant; D008297:Male; D000068557:Olmesartan Medoxomil; D013777:Tetrazoles / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil