الفهرس 
Title : Efficacy and pharmacokinetic study of daclatasvir in adolescents infected with hepatitis A preliminary study
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Abstract
Chronic hepatitis C virus (HCV) infection is responsible for liver fibrosis, liver cirrhosis, hepatocellular carcinoma (HCC), and the most common indication for liver transplantation worldwide. Daclatasvir, an oral antiviral drug, is an HCV non-structural protein 5A (NS5A) inhibitor.The objectives of this study were to study the efficacy and safety of daclatasvir in combination with sofosbuvir, to determine the noncompartmental pharmacokinetic parameters of daclatasvir and to develop a population pharmacokinetic model in adolescents aged 12-17 years and who weigh {u2265}35 kg with HCV genotype 4 in order to evaluate the appropriateness of the adult’s dose in adolescents. Moreover, to evaluate the presence of the baseline resistance-associated substitutions (RASs) to daclatasvir and changes in liver fibrosis and steatosis parameters in those patients.Blood samples for pharmacokinetic (PK) analysis were obtained at steady state. A pre-dose blood sample was collected up to 30 minutes prior to the intended dose, after which patients were administered daclatasvir 60 mg and sofosbuvir 400 mg. Post-dose blood samples were collected at 0.5, 1, 1.5, 2, 4, 8, 12 and 24-hours post-dose.The plasma concentration of daclatasvir was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 17 HCV adolescent patients completed the study with 151 plasma samples were included for population pharmacokinetic (PopPK) evaluation and statistical analysis. Overall, sustained virological response after 12 weeks of treatment (SVR12) was achieved by 100% of patients (17/17). The most commonly reported adverse events were abdominal pain (6%) and dizziness (6%).The average PK parameters calculated by non-compartmental analysis (NCA): Cmax, area under the curve (AUC), apparent volume of distribution (V/F), apparent oral clearance (CL/F) and half-life (t1/2) were 1.1æg/ml,11.2æg/ml*h, 55L, 4.5 L/h and 8.5 hours respectively