Effect of CYP3A4 genetic polymorphisms on pharmacokinetics of tinidazole

doi:10.5246/jcps.2020.04.026

Abstract

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: t_1/2: (15.92±1.62), (15.77±1.67) h; C_max: (18.72±3.10), (20.25±3.42) mg/L; t_max: (1.50±0.66), (1.45±0.69) h; V_d/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

CLC Number:

R945

Supporting:

Xinyu Chang, Tao Guo, Guiming Guo . Effect of CYP3A4 genetic polymorphisms on pharmacokinetics of tinidazole[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(4): 272-279.

References

[1] Escobedo, A.A.; Ballesteros, J.; González-Fraile, E.; Almirall, P. A meta-analysis of the efficacy of albendazole compared with tinidazole as treatments for Giardia infections in children. Acta Trop. 2016, 153, 120-127.

[2] Hajiani, E.; Alavinejad, P.; Avandi, N.; Masjedizadeh, A.R.; Shayesteh, A.A. Comparison of levofloxacin-based, 10-day sequential therapy with 14-day quadruple therapy for Helicobacter pylori eradication: A randomized clinical trial. Middle East J. Dig. Dis. 2018, 10, 242-248.

[3] Roure, S.; Valerio, L.; Soldevila, L.; Salvador, F.; Fernández-Rivas, G.; Sulleiro, E.; Mañosa, M.; Sopena, N.; Mate, J.L.; Clotet, B. Approach to amoebic colitis: Epidemiological, clinical and diagnostic considerations in a non-endemic context (Barcelona, 2007-2017). PLoS One. 2019, 14, e0212791.

[4] Baery, N.; Ghasemi Nejad, A.; Amin, M.; Mahroozade, S.; Mokaberinejad, R.; Bioos, S.; Anushiravani, M.; Aliasl, J.; Karimi Darmiyan, M.; Amin, G. Effect of vaginal suppository on bacterial vaginitis based on Persian medicine (Iranian traditional medicine): a randomised double blind clinical study. J. Obstet. Gynaecol. 2018, 38, 1110-1114.

[5] Wood, B.A.; Faulkner, J.K.; Monro, A.M. The pharmaco-kinetics, metabolism and tissue distribution of tinidazole. J. Antimicrob. Chemother. 1982, 10 Suppl A, 43-57.

[6] Viitanen, J.; Haataja, H.; Männistö, P.T. Concentrations of metronidazole and tinidazole in male genital tissues. Antimicrob. Agents Chemother. 1985, 28, 812-814.

[7] Männistö, P.; Karhunen, M.; Mattila, J.; Koskela, O.; Suikkari, A.M.; Heinonen, P.; Tuimala, R.; Haataja, H. Concentrations of metronidazole and tinidazole in female reproductive organs after a single intravenous infusion and after repeated oral administration. Infection. 1984, 12, 197-201.

[8] Ma, S.L.; Tang, N.L.S.; Wat, K.H.Y.; Tang, J.H.Y.; Lau, K.H.; Law, C.B.; Chiu, J.; Tam, C.C.W.; Poon, T.K.; Lin, K.L.; Kng, C.P.L.; Kong, H.L.; Chan, T.Y.; Chan, W.C.; Lam, L.C.W. Effect of CYP2D6 and CYP3A4 genotypes on the efficacy of cholinesterase inhibitors in southern Chinese patients with alzheimer's disease. Am. J. Alzheimers Dis. Other Demen. 2019, 34, 302-307.

[9] Guo, T.; Zuo, J.L.; Xia, D.Y.; Jia, L.H.; Xiao, Y.; Guo, H.L. Genetic polymorphism analysis of cytochrome P450(CYP)3A4, CYP2C9, CYP2C19 and CYP2D6 in Chinese Han and Hui population. Chin. J. Clin. Pharmaco. 2012, 28, 281-284.

[10] Li, X.Q.; Björkman, A.; Andersson, T.B.; Gustafsson, L.L.; Masimirembwa, C.M. Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur. J. Clin. Pharmacol. 2003, 59, 429-442.

[11] Wood, S.G.; John, B.A.; Chasseaud, L.F.; Brodie, R.R.; Baker, J.M.; Faulkner, J.K.; Wood, B.A.; Darragh, A.; Lambe, R.F. Pharmacokinetics and metabolism of 14C-tinidazole in humans. J. Antimicrob. Chemother. 1986, 17, 801-809.

[12] Yoon, S.H.; Cho, J.H.; Kwon, O.; Choi, J.Y.; Park, S.H.; Kim, Y.L.; Yoon, Y.R.; Won, D.I.; Kim, C.D. CYP3A and ABCB1 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of tacrolimus and its metabolites (M-I and M-III). Transplantation. 2013, 95, 828-834.

[13] Zhu, L.; Song, H.T.; Wang, Q.H.; Wu, W.Z.; Yang, S.L.; Tan, J.M. Effect of CYP3A4*18B, CYP3A5*3 gene polymorphism on dosage and concentration of tacrolimus in renal transplant patients. Acta Pharm. Sin. 2012, 47, 878-883.

[14] Yang, L.; Guo, T.; Zhuang, X.M.; Gu, H.Y. Influence of CYP2C9*2 genetic polymorphism on pharmacokinetics of losartan and its active metabolite E-3174 on the background of CYP3A4 wild genotype in healthy Chinese Hui subjects. J. Chin. Pharm. Sci. 2018, 2, 14-21.

[15] Zhang, J.; Dai, Y.; Liu, Z.H.; Zhang, M.X.; Li, C.; Chen, D.X.; Song, H.T. Effect of CYP3A4 and CYP3A5 genetic polymorphisms on the pharmacokinetics of sirolimus in healthy Chinese volunteers. Ther. Drug Monit. 2017, 39, 406-411.

[16] Bins, S.; Huitema, A.D.R.; Laven, P.; Bouazzaoui, S.E.; Yu, H.X.; van Erp, N.; van Herpen, C.; Hamberg, P.; Gelderblom, H.; Steeghs, N.; Sleijfer, S.; van Schaik, R.H.N.; Mathijssen, R.H.J.; Koolen, S.L.W. Impact of CYP3A4*22 on pazopanib pharmacokinetics in cancer patients. Clin. Pharmacokinet. 2019, 58, 651-658.

[17] Maddin, N.; Husin, A.; Gan, S.H.; Aziz, B.A.; Ankathil, R. Impact of CYP3A4*18 and CYP3A5*3 polymorphisms on imatinib mesylate response among chronic myeloid leukemia patients in Malaysia. Oncol. Ther. 2016, 4, 303-314.

[18] Wu, X.J.; Guo, T.; Zhang, F.Q.; Ma, R.; Zuo, J.L. Effect of CYP3A4*18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui subjects. J. Chin. Pharm. Sci. 2016, 25, 122-127.

[19] Chang, X.Y.; Guo, T.; Xia, D.Y. Pharmacokinetics of tinidazole in Chinese subjects: comparison of Mongolian, Korean, hui, Uighur and Han nationalities. J. Pharm. Pharm. Sci. 2009, 12, 175-180.