Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension

Masato Taguchi; Fukiko Ichida; Keiichi Hirono; Toshio Miyawaki; Naoki Yoshimura; Tsuneyuki Nakamura; Chisato Akita; Tomotaka Nakayama; Tsutomu Saji; Yuya Kato; Isao Horiuchi; Yukiya Hashimoto

doi:10.2133/dmpk.DMPK-10-RG-113

Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension

Masato Taguchi, Fukiko Ichida, Keiichi Hirono, Toshio Miyawaki, Naoki Yoshimura, Tsuneyuki Nakamura, Chisato Akita, Tomotaka Nakayama, Tsutomu Saji, Yuya Kato, Isao Horiuchi, Yukiya Hashimoto^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

We evaluated the pharmacokinetics of routinely administered bosentan in 46 Japanese pediatric patients with pulmonary arterial hypertension. Plasma samples were taken twice at times corresponding to the peak and trough concentrations following repetitive oral administration. The population pharmacokinetic parameters of bosentan were estimated by use of the NONMEM program, in which a onecompartment model with repetitive bolus dosing was parameterized in terms of the oral clearance (CL/F) and elimination rate constant (k). Polymorphisms of CYP3A5, SLCO1B1, SLCO1B3, and SLCO2B1 had no significant effect on the disposition of bosentan. In addition, the pharmacokinetics of bosentan was not altered by heart failure or coadministration of sildenafil. In contrast, weight (WT)-normalized values of CL/F were correlated negatively with age (AGE). The final population mean values of CL/F and k were estimated to be 0.409 · (1-0.0377 · (AGE-3.81)) · WT L/h and 0.175 h^-1, respectively.

Original language	English
Pages (from-to)	280-287
Number of pages	8
Journal	Drug Metabolism and Pharmacokinetics
Volume	26
Issue number	3
DOIs	https://doi.org/10.2133/dmpk.DMPK-10-RG-113
State	Published - 2011

Keywords

Bosentan
Cytochrome P450
Genetic polymorphisms
Organic anion transporting polypeptide
Pediatric patients
Pharmacokinetics
Pulmonary arterial hypertension

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science
Pharmacology (medical)

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10.2133/dmpk.DMPK-10-RG-113

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Taguchi, M., Ichida, F., Hirono, K., Miyawaki, T., Yoshimura, N., Nakamura, T., Akita, C., Nakayama, T., Saji, T., Kato, Y., Horiuchi, I., & Hashimoto, Y. (2011). Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension. Drug Metabolism and Pharmacokinetics, 26(3), 280-287. https://doi.org/10.2133/dmpk.DMPK-10-RG-113

@article{82cbb62f74434750bf9ee9928860dd95,

title = "Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension",

abstract = "We evaluated the pharmacokinetics of routinely administered bosentan in 46 Japanese pediatric patients with pulmonary arterial hypertension. Plasma samples were taken twice at times corresponding to the peak and trough concentrations following repetitive oral administration. The population pharmacokinetic parameters of bosentan were estimated by use of the NONMEM program, in which a onecompartment model with repetitive bolus dosing was parameterized in terms of the oral clearance (CL/F) and elimination rate constant (k). Polymorphisms of CYP3A5, SLCO1B1, SLCO1B3, and SLCO2B1 had no significant effect on the disposition of bosentan. In addition, the pharmacokinetics of bosentan was not altered by heart failure or coadministration of sildenafil. In contrast, weight (WT)-normalized values of CL/F were correlated negatively with age (AGE). The final population mean values of CL/F and k were estimated to be 0.409 · (1-0.0377 · (AGE-3.81)) · WT L/h and 0.175 h-1, respectively.",

keywords = "Bosentan, Cytochrome P450, Genetic polymorphisms, Organic anion transporting polypeptide, Pediatric patients, Pharmacokinetics, Pulmonary arterial hypertension",

author = "Masato Taguchi and Fukiko Ichida and Keiichi Hirono and Toshio Miyawaki and Naoki Yoshimura and Tsuneyuki Nakamura and Chisato Akita and Tomotaka Nakayama and Tsutomu Saji and Yuya Kato and Isao Horiuchi and Yukiya Hashimoto",

note = "Funding Information: Acknowledgements: This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Sciences ¤JSPS¥; from the Ministry of Education, Culture, Sports, Science and Technology of Japan ¤MEXT¥; and the Japan Research Foundation for Clinical Pharmacology.",

year = "2011",

doi = "10.2133/dmpk.DMPK-10-RG-113",

language = "英語",

volume = "26",

pages = "280--287",

journal = "Drug Metabolism and Pharmacokinetics",

issn = "1347-4367",

publisher = "Japanese Society for the Study of Xenobiotics",

number = "3",

}

Taguchi, M, Ichida, F, Hirono, K, Miyawaki, T, Yoshimura, N, Nakamura, T, Akita, C, Nakayama, T, Saji, T, Kato, Y, Horiuchi, I & Hashimoto, Y 2011, 'Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension', Drug Metabolism and Pharmacokinetics, vol. 26, no. 3, pp. 280-287. https://doi.org/10.2133/dmpk.DMPK-10-RG-113

TY - JOUR

T1 - Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension

AU - Taguchi, Masato

AU - Ichida, Fukiko

AU - Hirono, Keiichi

AU - Miyawaki, Toshio

AU - Yoshimura, Naoki

AU - Nakamura, Tsuneyuki

AU - Akita, Chisato

AU - Nakayama, Tomotaka

AU - Saji, Tsutomu

AU - Kato, Yuya

AU - Horiuchi, Isao

AU - Hashimoto, Yukiya

N1 - Funding Information: Acknowledgements: This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Sciences ¤JSPS¥; from the Ministry of Education, Culture, Sports, Science and Technology of Japan ¤MEXT¥; and the Japan Research Foundation for Clinical Pharmacology.

PY - 2011

Y1 - 2011

N2 - We evaluated the pharmacokinetics of routinely administered bosentan in 46 Japanese pediatric patients with pulmonary arterial hypertension. Plasma samples were taken twice at times corresponding to the peak and trough concentrations following repetitive oral administration. The population pharmacokinetic parameters of bosentan were estimated by use of the NONMEM program, in which a onecompartment model with repetitive bolus dosing was parameterized in terms of the oral clearance (CL/F) and elimination rate constant (k). Polymorphisms of CYP3A5, SLCO1B1, SLCO1B3, and SLCO2B1 had no significant effect on the disposition of bosentan. In addition, the pharmacokinetics of bosentan was not altered by heart failure or coadministration of sildenafil. In contrast, weight (WT)-normalized values of CL/F were correlated negatively with age (AGE). The final population mean values of CL/F and k were estimated to be 0.409 · (1-0.0377 · (AGE-3.81)) · WT L/h and 0.175 h-1, respectively.

AB - We evaluated the pharmacokinetics of routinely administered bosentan in 46 Japanese pediatric patients with pulmonary arterial hypertension. Plasma samples were taken twice at times corresponding to the peak and trough concentrations following repetitive oral administration. The population pharmacokinetic parameters of bosentan were estimated by use of the NONMEM program, in which a onecompartment model with repetitive bolus dosing was parameterized in terms of the oral clearance (CL/F) and elimination rate constant (k). Polymorphisms of CYP3A5, SLCO1B1, SLCO1B3, and SLCO2B1 had no significant effect on the disposition of bosentan. In addition, the pharmacokinetics of bosentan was not altered by heart failure or coadministration of sildenafil. In contrast, weight (WT)-normalized values of CL/F were correlated negatively with age (AGE). The final population mean values of CL/F and k were estimated to be 0.409 · (1-0.0377 · (AGE-3.81)) · WT L/h and 0.175 h-1, respectively.

KW - Bosentan

KW - Cytochrome P450

KW - Genetic polymorphisms

KW - Organic anion transporting polypeptide

KW - Pediatric patients

KW - Pharmacokinetics

KW - Pulmonary arterial hypertension

UR - http://www.scopus.com/inward/record.url?scp=79960000700&partnerID=8YFLogxK

U2 - 10.2133/dmpk.DMPK-10-RG-113

DO - 10.2133/dmpk.DMPK-10-RG-113

M3 - 学術論文

C2 - 21383523

AN - SCOPUS:79960000700

SN - 1347-4367

VL - 26

SP - 280

EP - 287

JO - Drug Metabolism and Pharmacokinetics

JF - Drug Metabolism and Pharmacokinetics

IS - 3

ER -

Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension

Abstract

Keywords

ASJC Scopus subject areas

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