title: Pharmacokinetics of drugs for pediatric pulmonary hypertension.
abstract: BACKGROUND
  Over the past few years, several drugs, each with a different mechanism, have been developed for the treatment of pulmonary hypertension (PH) and are now prescribed in the clinical setting. While the optimal doses of these drugs in adults have been determined, the optimal dose in children, however, is unclear. The aim of this study was therefore, to measure blood drug levels and analyze the pharmacokinetics of two such drugs in children.
  
  
  METHODS
  From April 2010 to May 2015, we prospectively enrolled 23 children with PH for treatment with bosentan and/or tadalafil. Twenty children were treated with bosentan and 19 received tadalafil. Sixteen children were given both drugs. Blood samples were collected after 2 weeks of treatment, and blood drug levels measured using high-performance liquid chromatography.
  
  
  RESULTS
  For both drugs, the peak plasma concentration was lower and the half-life was shorter than the known values in adults. The blood trough level of bosentan significantly correlated with its dose, but no such correlation was seen for tadalafil. For both drugs, no correlation was observed between age and blood drug levels.
  
  
  CONCLUSIONS
  Oral dosing with bosentan and tadalafil in children may not achieve therapeutic blood concentration. Thus, the optimal dosing must be established individually while monitoring blood drug level.
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Nakau
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Oka
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kajihama
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamagishi
authors.affiliation: Asahikawa Medical University Hospital Pharmacy, Asahikawa, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kamiyama
authors.affiliation: Asahikawa Medical University Hospital Pharmacy, Asahikawa, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tasaki
authors.affiliation: Department of Pediatrics, Abashiri-Kosei General Hospital, Abashiri, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kajino
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Azuma
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077300:Bosentan; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007223:Infant; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068581:Tadalafil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D058986:Phosphodiesterase 5 Inhibitors; D013449:Sulfonamides; D000068581:Tadalafil; D000077300:Bosentan
keywords: bosentan; pharmacokinetics; pulmonary hypertension; tadalafil