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A randomized study on the bioequivalence of desloratadine in Chinese healthy subjects and the association of different metabolic phenotypes with UGT2B10 and CYP2C8 genotypes

Author(s):

Suping Niu, Yan Li, Wenliang Dong, Lin Xia, Tiantian Shen, Jiaxue Wang, Qian Wang, Tan Zhang, Minjie Zhang, Gang Liu, Danjie Guo* and Yi Fang*   Pages 1 - 11 ( 11 )

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 was aimed to demonstrate bioequivalence between the test product (desloratadine tablet) and reference product AERIUS (5mg) both orally. And we directly examine the role of UGT2B10 and CYP2C8 genotypes in Chinese healthy subjects with different Desloratadine metabolic phenotypes.

Methods: It was a randomized, open-label, and four-sequence, single-dose crossover study conducted on 56 Chinese healthy 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 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.

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

Keywords:

Bioequivalence; desloratadine; 3-OH-desloratadine; metabolic phenotypes; UGT2B10; CYP2C8.

Affiliation:

Clinical Trial institution, Scientific Research Department, Peking University People's Hospital, Beijing, Department of Pharmacy, Jincheng General Hospital, Jincheng, Department of Pharmacy, Peking University People’s Hospital, Beijing, Department of Pharmacy, Peking University People’s Hospital, Beijing, Department of Pharmacy, Peking University People’s Hospital, Beijing, Department of Pharmacy, Peking University People’s Hospital, Beijing, Nursing Department,Peking University People’s Hospital, Beijing, Leiden Academic Center for Drug Research, Faculty of Science, Leiden University, Leiden, Beijing United-Power Pharma Tech Co. Ltd, Beijing, Department of Pharmacy, Peking University People’s Hospital, Beijing, Clinical Trial institution, Scientific Research Department, Peking University People's Hospital, Beijing, Department of Pharmacy, Peking University People’s Hospital, Beijing



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