A Randomized Study on the Bioequivalence of Desloratadine in Healthy Chinese Subjects and the Association of Different Metabolic Phenotypes With UGT2B10 and CYP2C8 Genotypes

Title:A Randomized Study on the Bioequivalence of Desloratadine in Healthy Chinese Subjects and the Association of Different Metabolic Phenotypes With UGT2B10 and CYP2C8 Genotypes

Volume: 21 Issue: 13

Author(s): Suping Niu, Yan Li, Wenliang Dong, Lin Xia, Tiantian Shen, Jiaxue Wang, Qian Wang, Tan Zhang, Minjie Zhang, Gang Liu, Danjie Guo*Yi Fang*

Affiliation:

• Scientific Research Department, Clinical Trial Institution, Peking University People's Hospital, Beijing,China

• Department of Pharmacy, Peking University People’s Hospital, Beijing,China

Keywords: Bioequivalence, desloratadine, 3-OH-desloratadine, metabolic phenotypes, UGT2B10, CYP2C8.

Abstract: Background: Desloratadine is a drug with a phenotypic polymorphism in metabolism and has been approved for use in many countries to treat allergic diseases. CYP2C8 and UGT2B10 are metabolic enzymes, which may be involved in the metabolism of desloratadine.

Objective: This study aimed to demonstrate bioequivalence between the test product (desloratadine tablet) and the reference product AERIUS (5mg), both orally administered. And the role of UGT2B10 and CYP2C8 genotypes in healthy Chinese subjects with different Desloratadine metabolic phenotypes was examined.

Methods: It was a randomized, open-label, and four-sequence, single-dose crossover study conducted on 56 healthy Chinese subjects. The pharmacokinetics (PK) and safety of the test and reference Desloratadine products were compared. UGT2B10 and CYP2C8 genotypes were determined by the TaqMan assay using genomic DNA. Multiple linear regression was applied to analyze the correlation between genotypes and the metabolic ratio.

Results: The mean serum concentration-time curves of desloratadine and 3-OH-desloratadine were similar between the test product and the reference product. For the PK similarity comparison, the 90% CIs for the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ of desloratadine and 3-OH-desloratadine of test and reference product were completely within 80-125%. None of all 56 subjects had serious adverse events. Only 2 subjects were poor-metabolizers in 56 healthy subjects. There was no significant correlation between investigated genotypes of CYP2C8 and UGT2B10 and the metabolic ratio.

Conclusion: The test desloratadine tablet was bioequivalent to the reference product. No direct relationship between CYP2C8 and UGT2B10 genotypes and desloratadine metabolic ratio was identified.

Cite this article as:

Niu Suping , Li Yan , Dong Wenliang , Xia Lin , Shen Tiantian , Wang Jiaxue , Wang Qian , Zhang Tan , Zhang Minjie , Liu Gang , Guo Danjie *, Fang Yi *, A Randomized Study on the Bioequivalence of Desloratadine in Healthy Chinese Subjects and the Association of Different Metabolic Phenotypes With UGT2B10 and CYP2C8 Genotypes, Current Drug Metabolism 2020; 21 (13) . https://dx.doi.org/10.2174/1389200221999201027143903

DOI https://dx.doi.org/10.2174/1389200221999201027143903	Print ISSN 1389-2002
Publisher Name Bentham Science Publisher	Online ISSN 1875-5453