Effects of Polymorphisms of the SLCO2B1 Transporter Gene on the Pharmacokinetics of Montelukast in Humans
- Authors
- Kim, Kyoung-Ah; Lee, Hye-Mi; Joo, Hyun-Jin; Park, In-Bae; Park, Ji-Young
- Issue Date
- 11월-2013
- Publisher
- WILEY
- Keywords
- montelukast; SLCO2B1; OATP2B1; pharmacogenetics; pharmacokinetics
- Citation
- JOURNAL OF CLINICAL PHARMACOLOGY, v.53, no.11, pp.1186 - 1193
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CLINICAL PHARMACOLOGY
- Volume
- 53
- Number
- 11
- Start Page
- 1186
- End Page
- 1193
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/101793
- DOI
- 10.1002/jcph.144
- ISSN
- 0091-2700
- Abstract
- Montelukast, a leukotriene receptor antagonist, is a substrate of organic anion transporting OATP2B1 encoded by the SLCO2B1. We evaluated the effects of six non-synonymous (c.1175C>T, c.1457C>T, c.43C>T, c.935G>A, c.601G>A, and c.644A>T) polymorphisms and one promoter (g.-282G>A) polymorphism on the pharmacokinetics of montelukast. A single dose of 10mg montelukast was administered in 24 healthy subjects. Its levels were measured up to 24hours and a pharmacokinetic analysis was performed based on the SLCO2B1 polymorphisms. We did not encounter subjects with c.1175C>T, c.43C>T, or c.644A>T polymorphisms. The remaining SLCO2B1 polymorphisms did not affect plasma levels of montelukast, and pharmacokinetic parameters of montelukast did not differ among genotype groups. Oral clearance results were as follows: (1) 3.3L/h for c.935GG, 3.0L/h for c.935GA, and 3.5L/h for c.935AA; (2) 3.4L/h for c.1457CC, 2.9L/h for c.1457CT, and 3.2L/h for c.1457TT; (3) 3.2L/h for c.601GG, 3.4L/h for c.601GA, and 3.4L/h for c.601AA; (4) 3.2L/h for g.-282GG, 3.4L/h for g.-282GA, and 3.2L/h for g.-282AA. The findings suggest that SLCO2B1 polymorphisms do not affect the pharmacokinetics of montelukast and that SLCO2B1 polymorphisms appear to be a minor determinant of inter-individual variability of montelukast.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.