About AVT
Browse Articles
Authors
Customer Services

Original article

Pharmacokinetics of daclatasvir in Egyptian adolescents with genotype-4 HCV infection

Mogeb M Al-Nahari, Maggie M Abbassi, Fatma SE Ebeid, Mohamed Hassany, Manal H El-Sayed, Samar F Farid

Corresponding author name: Maggie M Abbassi
Corresponding author e-mail: maggie.abbassi@pharma.cu.edu.eg

Citation: Antiviral Therapy 2020; 25:101-110
doi: 10.3851/IMP3357

Date accepted: 22 April 2020
Date published online: 05 May 2020

Abstract

Background: Daclatasvir has potent antiviral activity against HCV infection when used in combination with sofosbuvir, however, its pharmacokinetics have not been described in adolescents. The aim is to determine the pharmacokinetic parameters of daclatasvir in adolescents, and to develop a population pharmacokinetic (PopPK) model.

Methods: Seventeen adolescent patients with genotype-4 chronic HCV infection received once daily oral daclatasvir 60 mg in combination with 400 mg sofosbuvir for 12 weeks. Steady state concentrations were determined. Non-compartmental and population PK were determined.

Results: The average PK parameters calculated by non-compartmental analysis (NCA): maximum plasma concentration (Cmax), area under the curve (AUC), apparent oral volume of distribution (V/F), apparent oral clearance (CL/F) and half-life (T1/2) were 1,092 ng/ml, 11,178 ng/ml•h, 55 l, 4.5 l/h and 8.5 h, respectively. Daclatasvir was best described by one compartment structural PK model with zero order absorption and first-order elimination. The absorption rate constant (K0), V/F, and CL/F of the final PopPK model of daclatasvir were 1.5/h, 52 l and 4.7 l/h, respectively. Body weight and serum albumin had significant effect on the V/F parameter.

Conclusions: Body weight and serum albumin were the major determinants of daclatasvir V/F in this population. PK parameters were comparable to those reported in adult HCV patients, demonstrating that 60 mg daclatasvir is an appropriate dose for adolescents. ClinicalTrials.gov NCT03540212.

<< BACK

Copyright © 2021 Nucleus Holdings Ltd. Part of Nucleus Global.
Design and Technology by Nucleus Global
Company registration No. 321 0712 (England & Wales). Registered Office address: Admiral House 76-78 Old Street, London EC1V 9AZ.