Pharmacokinetics Study and Polymorphic Gene Expression in Response of Direct Antiviral Drug Therapy For HCV Genotypes

Abstract

Hepatitis C virus is the major cause of death for decades in Pakistan and one-third of the population lives with this disease, which is at risk for a healthy life. There are many antiviral drugs available in the market for the eradication of viral load from the patients but the success rate is low. Of course, there are new antiviral drugs available for HCV but no validation system exists for these drugs here in Pakistan. The chances of reoccurrence of the disease further worsen the situation. Differences in HCV genotypes and their response to different antiviral drugs show different efficacies of the antiviral therapies. A total of 100 HCV patients were selected for this study and after intake of a single dose of medicine both blood and urine samples were taken for urinary excretion, renal clearance and pharmacokinetics of antivirals (sofosbuvir, simeprevir, daclatasvir, and ribavirin). Genetic polymorphism near IL 28B and IL 10R gene was examined for each patient and its effect on treatment response was assessed. Pharmacokinetic parameters were studied average Cmax (ng/ml) for sofosbuvir, GS 331007, simeprevir, daclatasvir, and ribavirin were 746±261 1676±361, 2021±221, 640±102, 792±92, respectively and average Tmax(h) for sofosbuvir, GS 331007, simeprevir, daclatasvir, and ribavirin were 1.30±0.61, 3.30±0.91, 6.0±0.3, 2.3±0.4 and 1.8±0.2 respectively. AUC for sofosbuvir, GS 331007, simeprevir, daclatasvir, and ribavirin were 1036±212, 16300±401, 23750±201, 10834±405 and 13100±103 respectively. Urinary excretion and renal clearance were also studied about 85.31% sofosbuvir, 0.90% simeprevir, 93.90% daclatasvir, and 30.19% ribavirin was excreted through urine within 24 hours after intake of a single dose of medicine. The presence of T allele near IL 28B gene indicates less response or delayed response towards antiviral therapy and the presence of G allele near IL 10R gene has a similar role as IL 28B so treatment prediction was based on polymorphic gene expression of the patients treated acting antivirals. Genetic polymorphisms near the IL 10R gene and IL 28B seem to influence the clinical course and the response to antiviral treatment in patients with chronic hepatitis C, suggesting individualized follow-up and treatment strategies. Keywords: Chronic hepatitis C, Single nucleotide polymorphism, Hepatitis C virus infection, Interleukin 28B, Cmax, Area under the curve, Half-life.