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. Trial Registration: ClinicalTrials.gov identifier: NCT00151814.
[Show abstract][Hide abstract] ABSTRACT: Olmesartan medoxomil is a nonpeptide angiotensin II-type I receptor (AT1) antagonist with greater affinity for this receptor than other drugs in this class. Several clinical trials have demonstrated its efficacy in lowering blood pressure and its good tolerability. This drug has been compared in clinical trials with other drugs in the same class (azilsartan, candesartan, irbesartan, losartan and valsartan). In general, olmesartan administered orally at a dose of between 20 and 40 mg has provided superior efficacy in lowering blood pressure; this effect is initiated earlier than with other drugs and persists for 24 hours. The advantages of olmesartan have been confirmed by several meta-analyses. Some studies show organ protective properties, especially in restoring endothelial function. The pattern and frequency of adverse reactions are similar to those of placebo. As a result of its pharmacodynamic and pharmacokinetic properties, olmesartan could offer advantages over other angiotensin receptor antagonists in the treatment of hypertension.
Hipertensión y Riesgo Vascular 01/2013; 30:11–15. DOI:10.1016/S1889-1837(13)70014-X
[Show abstract][Hide abstract] ABSTRACT: In the United States, passage of the FDASIA legislation made BPCA and PREA permanent, no longer requiring reauthorization every 5 years. This landmark legislation also stressed the importance of performing clinical trials in neonates when appropriate. In Europe the Pediatric Regulation, which went into effect in early 2007, also provides a framework for expanding pediatric clinical research. Although much work remains, as a result of greater regulatory guidance more pediatric data are reaching product labels.
Advances in Pediatrics 08/2014; 61(1). DOI:10.1016/j.yapd.2014.03.005
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