Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers.

摘要: Mizolastine is a selective histamine H1 receptor antagonist for chronic urticaria or allergic rhinitis. We investigated whether the variant genotypes of metabolic enzymes UGT1A1, CYP3A5 and transporter ABCB1 influence pharmacokinetic phenotype substrate mizolastine in Chinese volunteers. Genotyping single nucleotide polymorphisms UGT1A1*6 (G211A), CYP3A5*3 (A6986G) (C3435T) was determined by pyrosequencing method. After oral dose 10 mg mizolastine, plasma concentrations were measured using validated high-performance liquid chromatography 24 healthy The results showed that distributions wild-type homozygotes allele carriers (the sum heterozygotes homozygotes) as follows: 17 cases (70.8%) versus seven (29.2%) genotypes, five (20.8%) 19 (79.2%) 3435T respectively. There no significant differences parameters between UGT1A1*6, homozygotes, ratios Cmax 101.03%, 86.02% 105.78%; Tmax 162.35%, 98.98% 144.90%; AUC0-28 113.04%, 77.35% 112.71%; t1/2 95.77%, 72.40% 100.97%, In conclusion, these suggested genetic might be not contributed to interindividual variation population.