Journal of Clinical & Experimental Pharmacology

CYP2E1 polymorphism, acetylator profiles and drug-induced liver injury incidence of Indonesian tuberculosis patients

8^th World Congress on Pharmacology and Toxicology

July 24-25, 2017 Melbourne, Australia

Dyah A Perwitasari, Lalu M Irham, Endang Darmawan, Ully A Mulyani and J Atthobari

Ahmad Dahlan University, Indonesia
National Institute for Health Research and Development, Indonesia
Universitas Gadjah Mada, Indonesia

Scientific Tracks Abstracts: Clin Exp Pharmacol

Abstract:

Statement of the Problem: India, Indonesia and China had the largest number of cases from global total number (23%, 10% and 10%, respectively). There are large variations in the metabolism of the anti-tuberculosis drug-isoniazid, including polymorphisms of the NAT2 gene. This enzyme is markedly decreased in the livers of Slow Acetylators (SA). The elimination of INH follows a bimodal or trimodal distribution consisting of slow (SA), intermediate (IA) and Rapid Acetylators (RA). There is a strong correlation between these phenotypes and NAT2 genotypes in Caucasians. Previous studies have reported inconsistent results on whether slow or rapid acetylators are a risk factor for INH-induced hepatotoxicity. The purpose of this study is to determine the association between CYP2E1 polymorphisms and the development of DILI in Indonesians and determine the genotypes and phenotypes related to a change in the risk of DILI. Methodology & Theoretical Orientation: A cohort design consisting of 55 Indonesian adult Tuberculosis (TB) patients was carried out. Acetylating phenotypes were studied using the metabolic ratio of plasma Ac HZ/HZ. DILI was defined using CTCAV version 4.0. The allelic and genotypic frequency distributions of CYP2E1 rs3813867 were studied using the polymerase chain reaction-amplification refractory mutation system (ARMS) methodology. Findings: Patients with an INH concentration of more than 7 mg/mL showed a higher risk of developing DILI when compared with patients who showed a therapeutic range of 3-6 mg/mL INH (OR: 1.3, 95% CI: 0.2-8.2). SAs had a higher incidence of DILI when compared with RAs (OR: 4.6, 95% CI: 1.3-15.9). Meanwhile, subjects with GC had a higher risk of DILI incidence (OR: 4.3, 95% CI: 0.8�??24.4). Conclusion & Significance: Our study shows that polymorphisms of CYP2E1 and SAs may have role in the DILI incidence. Recommendations are needed to be considered by the pharmacists during the adverse drug reaction monitoring.

Biography :

Dyah A Perwitasari has her expertise in pharmacogenetic and pharmaceutical care. She has developed a model of treatment monitoring according to the pharmacogenetic results study, the model which may improve patients’ quality of life by involving the psychological domains of patients. Thus, by combining the personalized medicine monitoring in pharmacogenetic science and assessing patients’ psychological factors, the results of her studies may clinically increase patient’s quality of life.

Email: da_perwitasari@uad.ac.id