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.
| Original language | English |
|---|---|
| Pages (from-to) | 1112-1117 |
| Number of pages | 6 |
| Journal | Pediatrics International |
| Volume | 58 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2016 Nov 1 |
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Keywords
- bosentan
- pharmacokinetics
- pulmonary hypertension
- tadalafil
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
Cite this
Pharmacokinetics of drugs for pediatric pulmonary hypertension. / Nakau, Kouichi; Sugimoto, Masaya; Oka, Hideharu; Kajihama, Aya; Maeda, Jun; Yamagishi, Hiroyuki; Kamiyama, Naoya; Tasaki, Yoshikazu; Kajino, Hiroki; Azuma, Hiroshi.
In: Pediatrics International, Vol. 58, No. 11, 01.11.2016, p. 1112-1117.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetics of drugs for pediatric pulmonary hypertension
AU - Nakau, Kouichi
AU - Sugimoto, Masaya
AU - Oka, Hideharu
AU - Kajihama, Aya
AU - Maeda, Jun
AU - Yamagishi, Hiroyuki
AU - Kamiyama, Naoya
AU - Tasaki, Yoshikazu
AU - Kajino, Hiroki
AU - Azuma, Hiroshi
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - bosentan
KW - pharmacokinetics
KW - pulmonary hypertension
KW - tadalafil
UR - http://www.scopus.com/inward/record.url?scp=84996587478&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84996587478&partnerID=8YFLogxK
U2 - 10.1111/ped.12997
DO - 10.1111/ped.12997
M3 - Article
VL - 58
SP - 1112
EP - 1117
JO - Pediatrics International
JF - Pediatrics International
SN - 1328-8067
IS - 11
ER -