Tham Hong Pham, Hieu Thi Minh Huynh, Ha Thi Vo, Hung Manh Tran
Tham Hong Pham1, Hieu Thi Minh Huynh1, Ha Thi Vo2, Hung Manh Tran3*
1Department of Pharmacy, Nhan Dan Gia Dinh Hospital, Ho Chi Minh City, V-700000, Vietnam.
2Faculty of Pharmacy, Pham Ngoc Thach University of Medicine, Ho Chi Minh, V-700000, Vietnam.
3Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh, V-700000, Vietnam.
Volume - 13,
Issue - 6,
Year - 2020
Objective: This study aims to investigate whether CYP3A5 polymorphisms affect steady-state carbamazepine (CBZ) concentrations and therapeutic effects of CBZ monotherapy in Vietnamese epileptic patients. Methods: A prospective study was conducted from December 2016 to June 2017 at Neurology Department at Nhan Dan Gia Dinh hospital, Vietnam. CBZ concentrations were measured using the fluorescence polarization immuno assay and CYP3A5 were genotyped using a polymerase chain reaction-restriction fragment length polymorphism. Results: Thirty-two patients were CYP3A5 expressors (twenty-three for CYP3A5 *1/*1 and nine for CYP3A5*1/*3) and six patients were CYP3A5 non-expressors (CYP3A5*3/*3). Dose normalized concentrations (mean ± SD) of CBZ were 7.9 ± 3.5 ng/mL/mg for CYP3A5 expressors and 8.1 ± 3.7 ng/mL/mg for CYP3A5 non-expressors. There was no statistically significant difference in efficacy between the two groups (?2 = 0.17, p = 0.37). A positive correlation between dose requirement of CBZ and serum level of CBZ was observed in both the CYP3A5 expressors (r = 0.28, p = 0.11) and the CYP3A5 non-expressors (r = 0.03, p = 0.95). However, when the concentration of CBZ normalized by the CBZ doses administered, a negative correlation was observed in both CYP3A5 expressors (r = 0.5, p = 0.004) and CYP3A5 non-expressors (r = 0.5, p = 0.33). Conclusion: The CYP3A5 genotype affected the CBZ concentrations in Vietnamese epileptic patients and is a factor that may contribute to the individual variability of CBZ efficacy in epileptic patients.
Cite this article:
Tham Hong Pham, Hieu Thi Minh Huynh, Ha Thi Vo, Hung Manh Tran. Effect of CYP3A5 genotypes on serum carbamazepine concentrations at steady-state in Vietnamese epileptic patients. Research J. Pharm. and Tech 2020; 13(6): 2802-2806. doi: 10.5958/0974-360X.2020.00498.9
Tham Hong Pham, Hieu Thi Minh Huynh, Ha Thi Vo, Hung Manh Tran. Effect of CYP3A5 genotypes on serum carbamazepine concentrations at steady-state in Vietnamese epileptic patients. Research J. Pharm. and Tech 2020; 13(6): 2802-2806. doi: 10.5958/0974-360X.2020.00498.9 Available on: https://rjptonline.org/AbstractView.aspx?PID=2020-13-6-48
1. Bauer LA. Carbamazepine in Applied clinical pharmacokinetics. 2nd ed. New York: McGraw-Hill; 2008. p. 548-61.
2. McAuley JW, McFadden LS, Elliott JO, Shneker BF. An evaluation of self-management behaviors and medication adherence in patients with epilepsy. Epilepsy Behav. 2008;13(4)(4):637-41.
3. Loscher W, Klotz U, Zimprich F, Schmidt D. The clinical impact of pharmacogenetics on the treatment of epilepsy. Epilepsia. 2009;50(1)(1):1-23.
4. Thorn CF, Leckband SG, Kelsoe J, Leeder JS, Muller DJ, Klein TE, et al. PharmGKB summary: carbamazepine pathway. Pharmacogenet Genomics. 2011;21(12):906-10.
5. Sisodiya SM, Goldstein DB. Drug resistance in epilepsy: more twists in the tale. Epilepsia. 2007; 48:2369–70.
6. Lopez-Garcia MA, Feria-Romero IA, Fernando-Serrano H, Escalante-Santiago D, Grijalva I, Orozco-Suarez S. Genetic polymorphisms associated with antiepileptic metabolism. Front Biosci (Elite Ed). 2014; 6:377-86.
7. Barry A, Levine M. A systematic review of the effect of CYP3A5 genotype on the apparent oral clearance of tacrolimus in renal transplant recipients. Ther Drug Monit. 2010;32(6):708-14.
8. Seo T, Nakada N, Ueda N, Hagiwara T, Hashimoto N, Nakagawa K. Effect of CYP3A5*3 on carbamazepine pharmacokinetics in Japanese patients with epilepsy. Clin Pharmacol Ther. 2006;79(5):509-10.
9. Park PW, Seo YH, Ahn JY, Kim KA, Park JY. Effect of CYP3A5*3 genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients. J Clin Pharm Ther. 2009;34(5):569-74.
10. Meng H, Ren J, Lv Y, Lin W, Guo Y. Association study of CYP3A5 genetic polymorphism with serum concentrations of carbamazepine in Chinese epilepsy patients. Neurology Asia. 2011;16(1):39-45.
11. Lu Q, Huang YT, Shu Y, Xu P, Xiang DX, Qu Q, et al. Effects of CYP3A5 and UGT2B7 variants on steady-state carbamazepine concentrations in Chinese epileptic patients. Medicine (Baltimore). 2018;97(30):e11662.
12. Panomvana D, Traiyawong T, Towanabut S. Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. J Pharm Pharm Sci. 2013;16(4):502-10.
13. Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Chadwick D, Guerreiro C, et al. ILAE Treatment Guidelines: Evidence-based Analysis of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures and Syndromes. Epilepsia. 2006;47(7):1094–120.
14. Veiga MI, Asimus S, Ferreira PE, Martins JP, Cavaco I, Ribeiro V, et al. Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam. Eur J Clin Pharmacol. 2009;65(4):355-63.
15. Seo T, Nakada N, Ueda N, Hagiwara T, Hashimoto N, Nakagawa K, et al. Effect of CYP3A5*3 on carbamazepine pharmacokinetics in Japanese patients with epilepsy. Clin Pharmacol Ther. 2006 May;79(5):509-10.
16. Park PW, Seo YH, Ahn JY, Kim KA, Park JY. Effect of CYP3A5*3 genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients. J Clin Pharm Ther. 2009 Oct;34(5):569-74.
17. Lu Q, Huang YT, Shu Y, Xu P, Xiang DX, Qu Q, et al. Effects of CYP3A5 and UGT2B7 variants on steady-state carbamazepine concentrations in Chinese epileptic patients. Medicine (Baltimore). 2018 Jul;97(30):e11662.
18. Kudriakova TB, Sirrota LA, Rozova GI, Gỏkov VA. Autoinduction and steady-state pharmacokinetics of cabamazepine and its major metabolites. British Journal of Clinical Pharmacology. 1992;33:611-5.