PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-19 (19)
 

Clipboard (0)
None

Select a Filter Below

Year of Publication
1.  Repair of congenital heart disease with associated pulmonary hypertension in children: what are the minimal investigative procedures? Consensus statement from the Congenital Heart Disease and Pediatric Task Forces, Pulmonary Vascular Research Institute (PVRI) 
Pulmonary Circulation  2014;4(2):330-341.
Standardization of the diagnostic routine for children with congenital heart disease associated with pulmonary arterial hypertension (PAH-CHD) is crucial, in particular since inappropriate assignment to repair of the cardiac lesions (e.g., surgical repair in patients with elevated pulmonary vascular resistance) may be detrimental and associated with poor outcomes. Thus, members of the Congenital Heart Disease and Pediatric Task Forces of the Pulmonary Vascular Research Institute decided to conduct a survey aimed at collecting expert opinion from different institutions in several countries, covering many aspects of the management of PAH-CHD, from clinical recognition to noninvasive and invasive diagnostic procedures and immediate postoperative support. In privileged communities, the vast majority of children with congenital cardiac shunts are now treated early in life, on the basis of noninvasive diagnostic evaluation, and have an uneventful postoperative course, with no residual PAH. However, a small percentage of patients (older at presentation, with extracardiac syndromes or absence of clinical features of increased pulmonary blood flow, thus suggesting elevated pulmonary vascular resistance) remain at a higher risk of complications and unfavorable outcomes. These patients need a more sophisticated diagnostic approach, including invasive procedures. The authors emphasize that decision making regarding operability is based not only on cardiac catheterization data but also on the complete diagnostic picture, which includes the clinical history, physical examination, and all aspects of noninvasive evaluation.
doi:10.1086/675995
PMCID: PMC4070778  PMID: 25006452
congenital heart disease; pulmonary hypertension; cardiac catheterization; pediatric cardiac surgery; postoperative care
3.  Effectiveness and Safety of Inhaled Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Children 
The American journal of cardiology  2012;110(11):1704-1709.
The introduction of prostanoid therapy has revolutionized the treatment of pulmonary arterial hypertension (PAH). However, continuous intravenous prostacyclin infusion poses significant risks and challenges, particularly in children. Inhaled treprostinil has been shown to be safe and efficacious in adults. This study describes the safety and efficacy of inhaled treprostinil in children with PAH. A retrospective analysis of 29 children, treated with inhaled treprostinil for ≥ 6 weeks was performed. Effects of inhaled treprostinil on exercise capacity, functional class, echocardiographic, and hemodynamic data were evaluated. Adverse events were documented. Patients received 3 - 9 breaths (6ucg/breath) of inhaled treprostinil 4 times daily. All were receiving background PH therapy; 12 had previously received parenteral prostanoid. Inhaled treprostinil was discontinued in 4 patients because of symptoms including cough and bronchospasm (3) and progression of PAH (1). Mild side effects including cough (9), sore throat(6) did not require discontinuation of therapy. The WHO functional class improved in 19 and was unchanged in 10; exercise capacity significantly improved, with the six minute walk distance (6MWD) improving on follow-up from 455.7+/-71.5 to 498+/-70 meters, (p=0.01) and peak oxygen consumption (pVO2) increasing from 25.5+/-10.2 to 27.4+/-10 (p=0.04). In conclusion, inhaled treprostinil was associated with improvement in exercise capacity and WHO functional class when added to background targeted PAH therapy in children, and had an acceptable safety profile. Based on these early data, further study of inhaled treprostinil appears warranted in pediatric PAH patients.
doi:10.1016/j.amjcard.2012.07.037
PMCID: PMC3508003  PMID: 22917554
pulmonary arterial hypertension; inhaled treprostinil; pediatric patients; safety and tolerability
4.  Moderate altitude is not associated with adverse postoperative outcomes for patients undergoing bidirectional cavopulmonary anastomosis and Fontan operation: A comparative study among Denver, Edmonton, and Toronto 
Objective
Outcomes of patients with single ventricle physiology undergoing cavopulmonary palliations depend on pulmonary vascular resistance (PVR) and have been suggested to be adversely affected by living at elevated altitude. We compared the pulmonary hemodynamic data in correlation with postoperative outcomes at the 3 centers of Denver, Edmonton, and Toronto at altitudes of 1604, 668, and 103 meters, respectively.
Methods
Hemodynamic data at pre-bidirectional cavopulmonary anastomosis (BCPA) and pre-Fontan catheterization between 1995 and 2007 were collected. Death from cardiac failure or heart transplantation in the same period was used to define palliation failure.
Results
There was no significant correlation between altitude (ranged from 1 to 2572 meters) and PVR, pulmonary artery pressure (PAP) or transpulmonary gradient (TPG) at pre-BCPA and pre-Fontan catheterization. BCPA failure occurred in 11 (9.2%) patients in Denver, 3 (2.9%) in Edmonton, and 34 (11.9%) in Toronto. Fontan failure occurred in 3 (6.1%) patients in Denver, 5 (7.2%) in Edmonton, and 11 (7.0%) in Toronto. There was no significant difference in BCPA and Fontan failure among the 3 centers. BCPA failure positively correlated with PVR and the presence of a right ventricle as the systemic ventricle. Fontan failure positively correlated with PAP and TPG.
Conclusions
Moderate altitude is not associated with an increased PVR or adverse outcomes in patients with a functional single ventricle undergoing BCPA and the Fontan operation. The risk factors for palliation failure are higher PVR, PAP, and TPG and a systemic right ventricle, but not altitude. Our study reemphasizes the importance of cardiac catheterization assessments of pulmonary hemodynamics before BCPA and Fontan operations.
doi:10.1016/j.jtcvs.2012.12.073
PMCID: PMC3800264  PMID: 23353110
5.  Advances in Pediatric Pulmonary Arterial Hypertension 
Current Opinion in Cardiology  2012;27(2):70-81.
Purpose of Review
Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in children. Approved medications for the treatment of adult PAH have been used to treat children but evidence based treatment algorithms for children are lacking.
Recent Findings
Pediatric PAH registries have begun to define the incidence and prevalence of idiopathic PAH and PAH associated with congenital heart disease. A pediatric specific classification of pulmonary hypertensive vascular disease has been proposed. Furthermore, the first randomized placebo-controlled trial of type-5 phosphodiesterase therapy in treatment naïve children with PAH has been completed and reported. This trial highlights the importance of the difficulties of performing clinical trials children with targeted PAH therapy as well as the importance of long-term follow-up of adverse events.
Summary
Classification, clinical trials, and therapy for children with PAH must take into account the unique aspects of PAH in children.
doi:10.1097/HCO.0b013e32835018cd
PMCID: PMC3319159  PMID: 22274573
Pulmonary Hypertension; Children; Endothelin Receptor Antagonists; Phosphodiesterase-5; Prostacyclin
6.  Clinical trials in neonates and children: Report of the pulmonary hypertension academic research consortium pediatric advisory committee 
Pulmonary Circulation  2013;3(1):252-266.
Drug trials in neonates and children with pulmonary hypertensive vascular disease pose unique but not insurmountable challenges. Childhood is defined by growth and development. Both may influence disease and outcomes of drug trials. The developing pulmonary vascular bed and airways may be subjected to maldevelopment, maladaptation, growth arrest, or dysregulation that influence the disease phenotype. Drug therapy is influenced by developmental changes in renal and hepatic blood flow, as well as in metabolic systems such as cytochrome P450. Drugs may affect children differently from adults, with different clearance, therapeutic levels and toxicities. Toxicity may not be manifested until the child reaches physical, endocrine and neurodevelopmental maturity. Adverse effects may be revealed in the next generation, should the development of ova or spermatozoa be affected. Consideration of safe, age-appropriate tablets and liquid formulations is an obvious but often neglected prerequisite to any pediatric drug trial. In designing a clinical trial, precise phenotyping and genotyping of disease is required to ensure appropriate and accurate inclusion and exclusion criteria. We need to explore physiologically based pharmacokinetic modeling and simulations together with statistical techniques to reduce sample size requirements. Clinical endpoints such as exercise capacity, using traditional classifications and testing cannot be applied routinely to children. Many lack the necessary neurodevelopmental skills and equipment may not be appropriate for use in children. Selection of endpoints appropriate to encompass the developmental spectrum from neonate to adolescent is particularly challenging. One possible solution is the development of composite outcome scores that include age and a developmentally specific functional classification, growth and development scores, exercise data, biomarkers and hemodynamics with repeated evaluation throughout the period of growth and development. In addition, although potentially costly, we recommend long-term continuation of blinded dose ranging after completion of the short-term, double-blind, placebo-controlled trial for side-effect surveillance, which should include neurodevelopmental and peripubertal monitoring. The search for robust evidence to guide safe therapy of children and neonates with pulmonary hypertensive vascular disease is a crucial and necessary goal.
doi:10.4103/2045-8932.109931
PMCID: PMC3641736  PMID: 23662203
drug toxicity; pediatrics; pulmonary vascular disease; pulmonary arterial hypertension; pulmonary hypertension with increased pulmonary vascular resistance
7.  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.
PMCID: PMC3527842  PMID: 23264720
pulmonary hypertension; children; endothelin receptor antagonists; phosphodiesterase-5; prostacyclin
8.  Morbidity of the Arterial Switch Operation 
The Annals of Thoracic Surgery  2012;93(6):1977-1983.
Background
The arterial switch operation (ASO) has become a safe, reproducible surgical procedure with low mortality in experienced centers. We examined morbidity, which remains significant, particularly for complex ASO.
Methods
From 2003 to 2011, 101 consecutive patients underwent ASO, arbitrarily classified as “simple” (n = 52) or “complex” (n = 49). Morbidity was measured in selected complications and postoperative hospitalization. Three outcomes were analyzed: ventilation time, postextubation hospital length of stay, and a composite morbidity index, defined as ventilation time + postextubation hospital length of stay + occurrence of selected major complications. Complexity was measured with the comprehensive Aristotle score.
Results
The operative mortality was zero. Twenty-five major complications occurred in 23 patients: 6 of 25 (12%) in simple ASO and 19 of 49 (39%) in complex ASO (p = 0.002). The most frequent complication was unplanned reoperation (15 vs 6, p = 0.03). No patients required permanent pacing. The complex group had a significantly higher morbidity index and longer ventilation time and postextubation hospital length of stay. In multivariate analysis, factors independently predicting higher morbidity were the comprehensive Aristotle score, arch repair, bypass time, and malaligned commissures. Myocardial infarction caused one sudden late death at 3 months. Late coronary failure was 2%. Overall survival was 99% at a mean follow-up of 49 ± 27 months.
Conclusions
In this consecutive series without operative mortality, morbidity was significantly higher in complex ASO. The only anatomic incremental risk factors for morbidity were aortic arch repair and malaligned commissures, but not primary diagnosis, weight less than 2.5 kg, or coronary patterns.
doi:10.1016/j.athoracsur.2011.11.061
PMCID: PMC3381339  PMID: 22365263
9.  Functional classification of pulmonary hypertension in children: Report from the PVRI pediatric taskforce, Panama 2011 
Pulmonary circulation  2011;1(2):280-285.
The members of the Pediatric Task Force of the Pulmonary Vascular Research Institute (PVRI) were aware of the need to develop a functional classification of pulmonary hypertension in children. The proposed classification follows the same pattern and uses the same criteria as the Dana Point pulmonary hypertension specific classification for adults. Modifications were necessary for children, since age, physical growth and maturation influences the way in which the functional effects of a disease are expressed. It is essential to encapsulate a child’s clinical status, to make it possible to review progress with time as he/she grows up, as consistently and as objectively as possible. Particularly in younger children we sought to include objective indicators such as thriving, need for supplemental feeds and the record of school or nursery attendance. This helps monitor the clinical course of events and response to treatment over the years. It also facilitates the development of treatment algorithms for children. We present a consensus paper on a functional classification system for children with pulmonary hypertension, discussed at the Annual Meeting of the PVRI in Panama City, February 2011.
doi:10.4103/2045-8932.83445
PMCID: PMC3161406  PMID: 21874157
pulmonary hypertension; children; functional class
10.  A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011 
Pulmonary circulation  2011;1(2):286-298.
Current classifications of pulmonary hypertension have contributed a great deal to our understanding of pulmonary vascular disease, facilitated drug trials, and improved our understanding of congenital heart disease in adult survivors. However, these classifications are not applicable readily to pediatric disease. The classification system that we propose is based firmly in clinical practice. The specific aims of this new system are to improve diagnostic strategies, to promote appropriate clinical investigation, to improve our understanding of disease pathogenesis, physiology and epidemiology, and to guide the development of human disease models in laboratory and animal studies. It should be also an educational resource. We emphasize the concepts of perinatal maladaptation, maldevelopment and pulmonary hypoplasia as causative factors in pediatric pulmonary hypertension. We highlight the importance of genetic, chromosomal and multiple congenital malformation syndromes in the presentation of pediatric pulmonary hypertension. We divide pediatric pulmonary hypertensive vascular disease into 10 broad categories.
doi:10.4103/2045-8932.83456
PMCID: PMC3161725  PMID: 21874158
pulmonary hypertension; pulmonary hypertension in the newborn; pulmonary vascular disease; pediatric patient
11.  Importance of the Clinical Recognition of Loeys-Dietz Syndrome in the Neonatal Period 
Pediatrics  2007;119(5):e1199-e1202.
We describe 5 patients who presented with musculoskeletal abnormalities in the neonatal period. All patients were initially suspected to have Larsen syndrome or Beals syndrome but were subsequently diagnosed with a TGFBR2 mutation diagnostic of Loeys-Dietz syndrome. Patients had progressive aortic enlargement, which necessitated surgical intervention for 3 patients and resulted in the death of 1 patient. Delay in diagnosis of Loeys-Dietz syndrome may be associated with adverse prognosis.
doi:10.1542/peds.2006-2886
PMCID: PMC3131201  PMID: 17470566
aortic aneurysm; aortic dissection; gene mutation
12.  Symptomatic Pulmonary Hypertension in a Child with Sickle Cell Disease 
The Journal of pediatrics  2008;152(6):879-881.
doi:10.1016/j.jpeds.2008.01.042
PMCID: PMC3128440  PMID: 18492535
13.  Functional classification of pulmonary hypertension in children: Report from the PVRI pediatric taskforce, Panama 2011 
Pulmonary Circulation  2011;1(2):280-285.
The members of the Pediatric Task Force of the Pulmonary Vascular Research Institute (PVRI) were aware of the need to develop a functional classification of pulmonary hypertension in children. The proposed classification follows the same pattern and uses the same criteria as the Dana Point pulmonary hypertension specific classification for adults. Modifications were necessary for children, since age, physical growth and maturation influences the way in which the functional effects of a disease are expressed. It is essential to encapsulate a child's clinical status, to make it possible to review progress with time as he/she grows up, as consistently and as objectively as possible. Particularly in younger children we sought to include objective indicators such as thriving, need for supplemental feeds and the record of school or nursery attendance. This helps monitor the clinical course of events and response to treatment over the years. It also facilitates the development of treatment algorithms for children. We present a consensus paper on a functional classification system for children with pulmonary hypertension, discussed at the Annual Meeting of the PVRI in Panama City, February 2011.
doi:10.4103/2045-8932.83445
PMCID: PMC3161406  PMID: 21874157
pulmonary hypertension; children; functional class
14.  A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011 
Pulmonary Circulation  2011;1(2):286-298.
Current classifications of pulmonary hypertension have contributed a great deal to our understanding of pulmonary vascular disease, facilitated drug trials, and improved our understanding of congenital heart disease in adult survivors. However, these classifications are not applicable readily to pediatric disease. The classification system that we propose is based firmly in clinical practice. The specific aims of this new system are to improve diagnostic strategies, to promote appropriate clinical investigation, to improve our understanding of disease pathogenesis, physiology and epidemiology, and to guide the development of human disease models in laboratory and animal studies. It should be also an educational resource. We emphasize the concepts of perinatal maladaptation, maldevelopment and pulmonary hypoplasia as causative factors in pediatric pulmonary hypertension. We highlight the importance of genetic, chromosomal and multiple congenital malformation syndromes in the presentation of pediatric pulmonary hypertension. We divide pediatric pulmonary hypertensive vascular disease into 10 broad categories.
doi:10.4103/2045-8932.83456
PMCID: PMC3161725  PMID: 21874158
pulmonary hypertension; pulmonary hypertension in the newborn; pulmonary vascular disease; pediatric patient
15.  Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice 
Human Molecular Genetics  2009;19(4):648-656.
Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, including an unprecedented high frequency of hypoplastic left heart syndrome (HLHS). We identified an ∼7 Mb ‘cardiac critical region’ in distal 11q that contains a putative causative gene(s) for congenital heart disease. In this study, we utilized chromosomal microarray mapping to characterize three patients with 11q- and congenital heart defects that carry interstitial deletions overlapping the 7 Mb cardiac critical region. We propose that this 1.2 Mb region of overlap harbors a gene(s) that causes at least a subset of the congenital heart defects that occur in 11q-. We demonstrate that one gene in this region, ETS-1 (a member of the ETS family of transcription factors), is expressed in the endocardium and neural crest during early mouse heart development. Gene-targeted deletion of ETS-1 in mice in a C57/B6 background causes, with high penetrance, large membranous ventricular septal defects and a bifid cardiac apex, and less frequently a non-apex-forming left ventricle (one of the hallmarks of HLHS). Our results implicate an important role for the ETS-1 transcription factor in mammalian heart development and should provide important insights into some of the most common forms of congenital heart disease.
doi:10.1093/hmg/ddp532
PMCID: PMC2807373  PMID: 19942620
16.  Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: the FUTURE-1 study 
AIM
To show equivalent bosentan exposure in paediatric patients with pulmonary arterial hypertension (PAH) when compared with a cohort of historical controls of adult PAH patients using a newly developed paediatric formulation.
METHODS
Thirty-six paediatric PAH patients were enrolled in this multicentre, prospective, open-label, noncontrolled study and treated for 4 weeks with bosentan 2 mg kg−1 b.i.d. and then for 8 weeks with 4 mg kg−1 b.i.d. Blood samples were taken for pharmacokinetic purposes. Exploratory efficacy measurements included World Health Organization (WHO) functional class and parent's and clinician's Global Clinical Impression scales.
RESULTS
Comparing children with a historical group of adults, the geometric mean ratio (90% confidence interval) of the area under the plasma concentration–time curve was 0.54 (0.37, 0.78), i.e. children had lower exposure to bosentan than adults. Bosentan concentrations following doses of 2 and 4 mg kg−1 were similar. Improvements in WHO functional class and the Global Clinical Impression scales occurred mainly in bosentan-naive patients, whereas the rare worsenings occurred in patients already on bosentan prior to study initiation. The paediatric formulation was well accepted and bosentan well tolerated in this study. No cases of elevated liver enzymes or anaemia were reported.
CONCLUSIONS
Exposure to bosentan, as shown comparing the results from this study with those from a study in adults, was different in paediatric and adult PAH patients. Since FUTURE-1 and past studies suggest a favourable benefit–risk profile for bosentan at 2 mg kg−1 b.i.d., this dose is recommended for children with PAH. The new paediatric formulation was well tolerated.
doi:10.1111/j.1365-2125.2009.03532.x
PMCID: PMC2805863  PMID: 20002090
bosentan; children; paediatric formulation; pharmacokinetics; pulmonary arterial hypertension
17.  Use of Myocardial Performance Index in Pediatric Patients with Idiopathic Pulmonary Arterial Hypertension 
Background
The myocardial performance index (MPI) correlates with clinical status in adults with idiopathic pulmonary arterial (PA) hypertension (IPAH). This pediatric study used MPI to assess response to bosentan therapy.
Methods
The study included 12 children with IPAH and 12 healthy control subjects. MPI was correlated with catheterization data at initiation of bosentan and at a median follow-up of 9 months. Therapy responders were defined by a greater than 20% decrease in mean PA pressure.
Results
Right ventricular MPI for patients with IPAH was 0.64 ± 0.30 versus 0.28 ± 0.03 in control subjects (P < .01). It had a strong correlation with mean PA pressure (R = 0.94; P < .001). Right ventricular MPI decreased significantly in responders (range 20%–44%, mean 25%) with a 5 % increase in nonresponders.
Conclusions
Right ventricular MPI in pediatric IPAH correlates with mean PA pressure and response to therapy. This study suggests that this noninvasive Doppler index may be useful to follow up children with IPAH, particularly when tricuspid regurgitation data are insufficient.
doi:10.1016/j.echo.2005.07.010
PMCID: PMC1934985  PMID: 16423665
18.  Perioperative Complications in Children with Pulmonary Hypertension Undergoing Noncardiac Surgery or Cardiac Catheterization 
Anesthesia and analgesia  2007;104(3):521-527.
BACKGROUND
Pulmonary arterial hypertension (PAH) can lead to significant cardiac dysfunction and is considered to be associated with an increased risk of perioperative cardiovascular complications.
METHODS
We reviewed the medical records of children with PAH who underwent anesthesia or sedation for noncardiac surgical procedures or cardiac catheterizations from 1999 to 2004. The incidence, type, and associated factors of complications occurring intraoperatively through 48 h postoperatively were examined.
RESULTS
Two hundred fifty-six procedures were performed in 156 patients (median age 4.0 yr). PAH etiology was 56% idiopathic (primary), 21% congenital heart disease, 14% chronic lung disease, 4% chronic airway obstruction, and 4% chronic liver disease. Baseline pulmonary artery pressure was subsystemic in 68% patients, systemic in 19%, and suprasystemic in 13%. The anesthetic techniques were 22% sedation, 58% general inhaled, 20% general IV. Minor complications occurred in eight patients (5.1% of patients, 3.1% of procedures). Major complications, including cardiac arrest and pulmonary hypertensive crisis, occurred in seven patients during cardiac catheterization procedures (4.5% of patients, 5.0% of cardiac catheterization procedures, 2.7% of all procedures). There were two deaths associated with pulmonary hypertensive crisis (1.3% of patients, 0.8% of procedures). Baseline supra-systemic PAH was a significant predictor of major complications by multivariate logistic regression analysis (OR = 8.1, P = 0.02). Complications were not significantly associated with age, etiology of PAH, type of anesthetic, or airway management.
CONCLUSION
Children with suprasystemic PAH have a significant risk of major perioperative complications, including cardiac arrest and pulmonary hypertensive crisis.
doi:10.1213/01.ane.0000255732.16057.1c
PMCID: PMC1934984  PMID: 17312201
19.  Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: the FUTURE-1 study 
AIM
To show equivalent bosentan exposure in paediatric patients with pulmonary arterial hypertension (PAH) when compared with a cohort of historical controls of adult PAH patients using a newly developed paediatric formulation.
METHODS
Thirty-six paediatric PAH patients were enrolled in this multicentre, prospective, open-label, noncontrolled study and treated for 4 weeks with bosentan 2 mg kg−1 b.i.d. and then for 8 weeks with 4 mg kg−1 b.i.d. Blood samples were taken for pharmacokinetic purposes. Exploratory efficacy measurements included World Health Organization (WHO) functional class and parent's and clinician's Global Clinical Impression scales.
RESULTS
Comparing children with a historical group of adults, the geometric mean ratio (90% confidence interval) of the area under the plasma concentration–time curve was 0.54 (0.37, 0.78), i.e. children had lower exposure to bosentan than adults. Bosentan concentrations following doses of 2 and 4 mg kg−1 were similar. Improvements in WHO functional class and the Global Clinical Impression scales occurred mainly in bosentan-naive patients, whereas the rare worsenings occurred in patients already on bosentan prior to study initiation. The paediatric formulation was well accepted and bosentan well tolerated in this study. No cases of elevated liver enzymes or anaemia were reported.
CONCLUSIONS
Exposure to bosentan, as shown comparing the results from this study with those from a study in adults, was different in paediatric and adult PAH patients. Since FUTURE-1 and past studies suggest a favourable benefit–risk profile for bosentan at 2 mg kg−1 b.i.d., this dose is recommended for children with PAH. The new paediatric formulation was well tolerated.
doi:10.1111/j.1365-2125.2009.03532.x
PMCID: PMC2805863  PMID: 20002090
bosentan; children; paediatric formulation; pharmacokinetics; pulmonary arterial hypertension

Results 1-19 (19)