title: Safety and efficacy of Sildenafil therapy in children with pulmonary hypertension.
abstract: OBJECTIVE
  Sildenafil is a selective Phosphodiesterase-5 inhibitor that has been reported to be a potent pulmonary vasodilator. We evaluated the safety, efficacy and pharmacokinetics of oral Sildenafil in a case series of children with pulmonary hypertension.
  
  
  METHODS
  Three children, 1 with primary pulmonary hypertension (patient 1) and 2 with pulmonary hypertension associated with congenital heart disease (patients 2 and 3) were enrolled. Sildenafil was started at 0.5 mg/kg 4-hourly and the dose increased to 1.0 and then to 2.0 mg/kg/dose. Patients were assessed at baseline and then monthly for a total of 6 visits.
  
  
  RESULTS
  All patients reported increased exercise capacity with improvement in New York Heart Association functional class. The distance walked during the 6-min test increased by 74% (patient 1), 75% (patient 2) and 25% (patient 3) and oxyhaemoglobin saturations increased from 79%, 97% and 80% to 93%, 100% and 93%, respectively. There were no side effects and no fall in systemic blood pressure. Sildenafil plasma levels 1 h after a 0.5, 1.0 and 2 mg/kg dose of Sildenafil were 109+/-87, 150+/-62 and 368+/-200 ng/ml, respectively. They fell to 211+/-106 ng/ml 3 h after the 2.0 mg/kg dose.
  
  
  CONCLUSIONS
  Medium term Sildenafil therapy improves oxyhaemoglobin saturations and exercise tolerance in children with pulmonary hypertension without any side effects. Mean plasma levels 1 h after doses of 0.5-2.0 mg/kg are similar to the maximum plasma concentrations reported in adults receiving doses within the therapeutic range. Sildenafil use in children appears to be safe and may be beneficial in the management of pulmonary arterial hypertension.
authors.affiliation: Department of Paediatric Cardiology, Royal Brompton Hospital, London, UK.
authors.forename: Ageliki A
authors.initials: AA
authors.lastname: Karatza
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
authors.forename: Alan G
authors.initials: AG
authors.lastname: Magee
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002908:Chronic Disease; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011687:Purines; D012449:Safety; D000068677:Sildenafil Citrate; D013450:Sulfones
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate