الفهرس 
Title : Pharmacokinetics of Sofosbuvir and Ledipasvir in Hepatitis C VirusInfected Adolescent Patients with Haematological Disorder
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Abstract
Background: Hepatitis C virus (HCV) comprises a worldwide health burden to which a macro-elimination program has been set and implemented. Beta-thalassemia major (BTM) is considered the most common chronic genetic haemolytic blood disorder in Egypt with annual birth rate of 1000/1.5 million live births. HCV infection affects about three and half million adolescents. BTM is considered a potential population for HCV micro-elimination model development since they are at high risk of multi-transfusion-acquired-HCV and are at higher risk of HCV complications. Sofosbuvir (SOF)/ledipasvir (LED) 400/90 mg for 12 weeks was found to have 98-100% success rate of HCV cure in adolescents. SOF/LED success rate sometimes differs in special sub-populations. BTM may negatively impact the pharmacokinetic (PK) exposure parameters of SOF/LED since SOF is metabolised in the red blood cells into GS-331007 whose exposure was strongly correlated to SOF antiviral activity. BTM patients usually show compensatory hyperdynamic state. Therefore, it was expected that LED and GS331007 exposure would be affected since their clearance is dependent on the hepatic and renal blood flow, respectively. Objectives: This study aimed at studying the effect of BTM on SOF/LED and SOF metabolite (GS-331007) pharmacokinetics. A second objective was the prediction of drug systemic exposure before therapy initiation. In addition, developing a predictive PK model of SOF/LED disposition in such a population and finally proposing any necessary dose adjustment in BTM patients to achieve maximum safety and efficacy