Pharmacokinetics of a Single Dose of Azilsartan in Pediatric Patients: A Phase 3, Open-Label, Multicenter Study.

INTRODUCTION: Azilsartan is an angiotensin II receptor blocker indicated for the treatment of patients with hypertension. The efficacy and safety of azilsartan are established in adults, but have not been evaluated in pediatric patients, nor has its pharmacokinetic profile been determined in pediatric patients. METHODS: In this phase 3, open-label, multicenter study, we investigated the pharmacokinetics and safety of single doses of azilsartan in six Japanese patients with hypertension, aged 9-14 years. The dose of azilsartan was 5 mg for three patients weighing less than 50 kg, with mean body weight at baseline of 27.5 kg, and 10 mg for three patients weighing at least 50 kg, with mean body weight at baseline of 65.9 kg. RESULTS: Mean maximum plasma concentration (Cmax) of azilsartan was 888.3 and 831.3 ng/mL and median time to maximum concentration (Tmax) of unchanged azilsartan was 3.0 and 4.0 h, in the 5-mg and 10-mg groups, respectively. Mean areas under the plasma concentration-time curve (AUC) from 0-24 h post-dose (AUC0-24) and 0 h to infinity (AUC0-inf) were 6350.3 and 6635.7 ng h/mL, respectively, in the 5-mg group, and 6871.7 and 7433.3 ng h/mL, respectively, in the 10-mg group. Both doses were well tolerated; no treatment-emergent adverse events considered to be related to azilsartan occurred during the study. CONCLUSION: Our data suggest that pediatric patients weighing less than 50 kg may have approximately 2-fold greater exposure to azilsartan than those weighing at least 50 kg at the same dose. Exposure to azilsartan in children weighing at least 50 kg is comparable to that in healthy adults at the same dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02451150. FUNDING: Takeda Pharmaceutical Co. Ltd.

A New Era in Medical Management of Severe Pediatric Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease whose prognosis has changed dramatically over the past decade since the introduction of new therapeutic agents as well as the off-label application of adult pulmonary hypertension specific therapies to children. Nevertheless, PAH still has no cure and the aim of treatment is to prolong survival by improving quality of life, symptoms, exercise capacity and hemodynamics. The selection of appropriate therapies for PH is complex and must be carefully chosen according to the etiology and pulmonary vasoreactivity. As insight advances into mechanisms responsible for the development of PAH, the introduction of novel therapeutic agents will hopefully further improve the outcome of this incurable disease.