In:
Basic & Clinical Pharmacology & Toxicology, Wiley, Vol. 123, No. 4 ( 2018-10), p. 464-473
Abstract:
Mizolastine is a selective histamine H1 receptor antagonist for chronic urticaria or allergic rhinitis. We investigated whether the variant genotypes of metabolic enzymes UGT 1A1, CYP 3A5 and transporter ABCB 1 influence pharmacokinetic phenotype of substrate mizolastine in Chinese volunteers. Genotyping of single nucleotide polymorphisms in UGT 1A1*6 ( G211A ), CYP 3A5*3 ( A6986G ) and ABCB 1 ( C3435T ) was determined by the pyrosequencing method. After a single oral dose of 10 mg mizolastine, the plasma concentrations were measured using validated high‐performance liquid chromatography in 24 Chinese healthy volunteers. The results showed that the distributions of wild‐type homozygotes and variant allele carriers (the sum of variant heterozygotes and variant homozygotes) were as follows: 17 cases (70.8%) versus seven cases (29.2%) in UGT 1A1*6 genotypes, five cases (20.8%) versus 19 cases (79.2%) in CYP 3A5*3 genotypes and seven cases (29.2%) versus 17 cases (70.8%) in ABCB 1 3435T genotypes, respectively. There were no significant differences in pharmacokinetic parameters of mizolastine between the variant allele UGT 1A1*6 , CYP 3A5*3 and ABCB 1 3435T carriers and the wild‐type homozygotes, and the ratios were as follows: C max was 101.03%, 86.02% and 105.78%; T max was 162.35%, 98.98% and 144.90%; AUC 0–28 was 113.04%, 77.35% and 112.71%; and t 1/2 was 95.77%, 72.40% and 100.97%, respectively. In conclusion, these results suggested that the UGT 1A1 , CYP 3A5 and ABCB 1 genetic polymorphisms might be not contributed to the interindividual variation of mizolastine pharmacokinetic phenotype in the Chinese population.
Type of Medium:
Online Resource
ISSN:
1742-7835
,
1742-7843
DOI:
10.1111/bcpt.2018.123.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2151592-X
detail.hit.zdb_id:
2134679-3
SSG:
15,3
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