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Journal of Chinese Pharmaceutical Sciences ›› 2020, Vol. 29 ›› Issue (4): 272-279.DOI: 10.5246/jcps.2020.04.026

• Original articles • Previous Articles     Next Articles

Effect of CYP3A4 genetic polymorphisms on pharmacokinetics of tinidazole

Xinyu Chang1*, Tao Guo2, Guiming Guo1   

  1. 1. Department of Clinical Pharmacy, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing100038, China
    2. Department of Pharmacy, the General Hospital of Shenyang Military Region, Shenyang 110015, China
  • Received:2019-11-25 Revised:2019-12-06 Online:2020-04-30 Published:2020-01-10
  • Contact: Tel.: +86-10-52177321, E-mail: xinyu_chang@163.com
  • Supported by:
    The Research Grant from the 115 Project of Legionary Medical Treatment and Public Health (Grant No. 06G023).

Abstract:

In the present study, we aimed to investigate the frequency of CYP3A4*18B genetic polymorphism in Han Chinese populations, and to assess the effect of the CYP3A4*18B genetic polymorphism on the pharmacokinetics of tinidazole. A total of 100 healthy volunteers from Han nationalities in China were recruited. DNA was extracted from peripheral leukocytes using a standard protocol. A PCR-RFLP method was developed to detect the alleles of CYP3A4*18B. A pharmacokinetic study of tinidazole was then carried out in two groups with CYP3A4*1/*1 (n = 10) and CYP3A4*1/*18B (n = 9) genotypes. Concentrations of tinidazole were determined using high-performance liquid chromatography in plasma samples that were collected up to 72 h after drug intake. In this study, 88 healthy volunteers were found with CYP3A4*1/*1 genotype, and 12 were found with CYP3A4*1/*18Bgenotype. CYP3A4*18B/*18B were absent from all subjects. The allele frequencies of CYP3A4*18B were 6%. The pharmacokinetic parameters of CYP3A4*1/*1 genotype and CYP3A4*1/*18B genotype in healthy subjects were as follows: t1/2: (15.92±1.62), (15.77±1.67) h; Cmax: (18.72±3.10), (20.25±3.42) mg/L; tmax: (1.50±0.66), (1.45±0.69) h; Vd/F: (55.73±10.66), (51.30±7.75) L; CL/F: (2.44±0.47), (2.26±0.30) L·h; AUC0: (424.40±82.38), (450.53±69.48) mg·h/L. Collectively, the CYP3A4*18B genetic polymorphism did not affect pharmacokinetics of tinidazolein healthy volunteers.

Key words: Tinidazole, CYP3A4, Pharmacokinetics

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