Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics

Koichiro Asano, Susumu Nakade, Tetsuya Shiomi, Takeshi Nakajima, Yusuke Suzuki, Koichi Fukunaga, Tsuyoshi Oguma, Koichi Sayama, Hirofumi Fujita, Yusuke Tanigawara, Akitoshi Ishizaka

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background and objective: Wide inter-individual variability in therapeutic effects limits the efficacy of leukotriene (LT) receptor antagonists in the treatment of asthma. We have reported that genetic variability in the expression of LTC4 synthase is associated with responsiveness to pranlukast in Japanese asthmatic patients. However, the effects of pharmacokinetic variability are less well known. This was an analysis of the pharmacokinetics of pranlukast in a population of adult asthmatics, and its effect on clinical responses. Other factors that may be related to the therapeutic effects of pranlukast, including LTC4 synthase gene polymorphisms, were also investigated. Methods: The population pharmacokinetics of pranlukast was analysed in a one-compartment model, using data collected in 50 Japanese adults with moderate to severe asthma, who were treated with pranlukast, 225 mg bd for 4 days. In 32 of these patients, in whom the clinical response to pranlukast (increase in FEV1 after 4 weeks of treatment) was measured in a previous study, a combined pharmacokinetic and pharmacogenetic analysis was performed. Results: Using the population pharmacokinetic model, the estimated the mean oral clearance (CL/F) of pranlukast was 16.4 L/h, and the inter-individual variability was 30.1%. Univariate and multivariate analyses showed that LTC 4 synthase polymorphisms, but not the CL/F of the drug, predicted an improvement in pulmonary function with pranlukast treatment (P < 0.05). Conclusions: There was marked inter-individual variability in the pharmacokinetics of pranlukast among adult asthmatics, but this had little impact on the clinical effectiveness of the drug.

Original languageEnglish
Pages (from-to)822-827
Number of pages6
JournalRespirology
Volume14
Issue number6
DOIs
Publication statusPublished - 2009 Aug

Fingerprint

Pharmacogenetics
Pharmacokinetics
Therapeutic Uses
Asthma
Population
Leukotriene Antagonists
pranlukast
Pharmaceutical Preparations
Therapeutics
Multivariate Analysis
Lung

Keywords

  • Asthma
  • Leucotriene
  • Leukotriene C synthase
  • Pharmacogenetics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics. / Asano, Koichiro; Nakade, Susumu; Shiomi, Tetsuya; Nakajima, Takeshi; Suzuki, Yusuke; Fukunaga, Koichi; Oguma, Tsuyoshi; Sayama, Koichi; Fujita, Hirofumi; Tanigawara, Yusuke; Ishizaka, Akitoshi.

In: Respirology, Vol. 14, No. 6, 08.2009, p. 822-827.

Research output: Contribution to journalArticle

Asano, K, Nakade, S, Shiomi, T, Nakajima, T, Suzuki, Y, Fukunaga, K, Oguma, T, Sayama, K, Fujita, H, Tanigawara, Y & Ishizaka, A 2009, 'Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics', Respirology, vol. 14, no. 6, pp. 822-827. https://doi.org/10.1111/j.1440-1843.2009.01552.x
Asano, Koichiro ; Nakade, Susumu ; Shiomi, Tetsuya ; Nakajima, Takeshi ; Suzuki, Yusuke ; Fukunaga, Koichi ; Oguma, Tsuyoshi ; Sayama, Koichi ; Fujita, Hirofumi ; Tanigawara, Yusuke ; Ishizaka, Akitoshi. / Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics. In: Respirology. 2009 ; Vol. 14, No. 6. pp. 822-827.
@article{c4acf565893646639b3736474faed945,
title = "Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics",
abstract = "Background and objective: Wide inter-individual variability in therapeutic effects limits the efficacy of leukotriene (LT) receptor antagonists in the treatment of asthma. We have reported that genetic variability in the expression of LTC4 synthase is associated with responsiveness to pranlukast in Japanese asthmatic patients. However, the effects of pharmacokinetic variability are less well known. This was an analysis of the pharmacokinetics of pranlukast in a population of adult asthmatics, and its effect on clinical responses. Other factors that may be related to the therapeutic effects of pranlukast, including LTC4 synthase gene polymorphisms, were also investigated. Methods: The population pharmacokinetics of pranlukast was analysed in a one-compartment model, using data collected in 50 Japanese adults with moderate to severe asthma, who were treated with pranlukast, 225 mg bd for 4 days. In 32 of these patients, in whom the clinical response to pranlukast (increase in FEV1 after 4 weeks of treatment) was measured in a previous study, a combined pharmacokinetic and pharmacogenetic analysis was performed. Results: Using the population pharmacokinetic model, the estimated the mean oral clearance (CL/F) of pranlukast was 16.4 L/h, and the inter-individual variability was 30.1{\%}. Univariate and multivariate analyses showed that LTC 4 synthase polymorphisms, but not the CL/F of the drug, predicted an improvement in pulmonary function with pranlukast treatment (P < 0.05). Conclusions: There was marked inter-individual variability in the pharmacokinetics of pranlukast among adult asthmatics, but this had little impact on the clinical effectiveness of the drug.",
keywords = "Asthma, Leucotriene, Leukotriene C synthase, Pharmacogenetics, Pharmacokinetics",
author = "Koichiro Asano and Susumu Nakade and Tetsuya Shiomi and Takeshi Nakajima and Yusuke Suzuki and Koichi Fukunaga and Tsuyoshi Oguma and Koichi Sayama and Hirofumi Fujita and Yusuke Tanigawara and Akitoshi Ishizaka",
year = "2009",
month = "8",
doi = "10.1111/j.1440-1843.2009.01552.x",
language = "English",
volume = "14",
pages = "822--827",
journal = "Respirology",
issn = "1323-7799",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics

AU - Asano, Koichiro

AU - Nakade, Susumu

AU - Shiomi, Tetsuya

AU - Nakajima, Takeshi

AU - Suzuki, Yusuke

AU - Fukunaga, Koichi

AU - Oguma, Tsuyoshi

AU - Sayama, Koichi

AU - Fujita, Hirofumi

AU - Tanigawara, Yusuke

AU - Ishizaka, Akitoshi

PY - 2009/8

Y1 - 2009/8

N2 - Background and objective: Wide inter-individual variability in therapeutic effects limits the efficacy of leukotriene (LT) receptor antagonists in the treatment of asthma. We have reported that genetic variability in the expression of LTC4 synthase is associated with responsiveness to pranlukast in Japanese asthmatic patients. However, the effects of pharmacokinetic variability are less well known. This was an analysis of the pharmacokinetics of pranlukast in a population of adult asthmatics, and its effect on clinical responses. Other factors that may be related to the therapeutic effects of pranlukast, including LTC4 synthase gene polymorphisms, were also investigated. Methods: The population pharmacokinetics of pranlukast was analysed in a one-compartment model, using data collected in 50 Japanese adults with moderate to severe asthma, who were treated with pranlukast, 225 mg bd for 4 days. In 32 of these patients, in whom the clinical response to pranlukast (increase in FEV1 after 4 weeks of treatment) was measured in a previous study, a combined pharmacokinetic and pharmacogenetic analysis was performed. Results: Using the population pharmacokinetic model, the estimated the mean oral clearance (CL/F) of pranlukast was 16.4 L/h, and the inter-individual variability was 30.1%. Univariate and multivariate analyses showed that LTC 4 synthase polymorphisms, but not the CL/F of the drug, predicted an improvement in pulmonary function with pranlukast treatment (P < 0.05). Conclusions: There was marked inter-individual variability in the pharmacokinetics of pranlukast among adult asthmatics, but this had little impact on the clinical effectiveness of the drug.

AB - Background and objective: Wide inter-individual variability in therapeutic effects limits the efficacy of leukotriene (LT) receptor antagonists in the treatment of asthma. We have reported that genetic variability in the expression of LTC4 synthase is associated with responsiveness to pranlukast in Japanese asthmatic patients. However, the effects of pharmacokinetic variability are less well known. This was an analysis of the pharmacokinetics of pranlukast in a population of adult asthmatics, and its effect on clinical responses. Other factors that may be related to the therapeutic effects of pranlukast, including LTC4 synthase gene polymorphisms, were also investigated. Methods: The population pharmacokinetics of pranlukast was analysed in a one-compartment model, using data collected in 50 Japanese adults with moderate to severe asthma, who were treated with pranlukast, 225 mg bd for 4 days. In 32 of these patients, in whom the clinical response to pranlukast (increase in FEV1 after 4 weeks of treatment) was measured in a previous study, a combined pharmacokinetic and pharmacogenetic analysis was performed. Results: Using the population pharmacokinetic model, the estimated the mean oral clearance (CL/F) of pranlukast was 16.4 L/h, and the inter-individual variability was 30.1%. Univariate and multivariate analyses showed that LTC 4 synthase polymorphisms, but not the CL/F of the drug, predicted an improvement in pulmonary function with pranlukast treatment (P < 0.05). Conclusions: There was marked inter-individual variability in the pharmacokinetics of pranlukast among adult asthmatics, but this had little impact on the clinical effectiveness of the drug.

KW - Asthma

KW - Leucotriene

KW - Leukotriene C synthase

KW - Pharmacogenetics

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=69049085653&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69049085653&partnerID=8YFLogxK

U2 - 10.1111/j.1440-1843.2009.01552.x

DO - 10.1111/j.1440-1843.2009.01552.x

M3 - Article

VL - 14

SP - 822

EP - 827

JO - Respirology

JF - Respirology

SN - 1323-7799

IS - 6

ER -