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Pharmacokinetics of drugs for pediatric pulmonary hypertension
Author(s) -
Nakau Kouichi,
Sugimoto Masaya,
Oka Hideharu,
Kajihama Aya,
Maeda Jun,
Yamagishi Hiroyuki,
Kamiyama Naoya,
Tasaki Yoshikazu,
Kajino Hiroki,
Azuma Hiroshi
Publication year - 2016
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/ped.12997
Subject(s) - medicine , tadalafil , bosentan , pharmacokinetics , dosing , drug , pharmacology , pulmonary hypertension , sildenafil , endothelin receptor , receptor
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.