Modelling the impact of JNJ-1802, a first-in-class dengue inhibitor blocking the NS3-NS4B interaction, on in-vitro DENV-2 dynamics.

Dengue virus (DENV) is a public health challenge across the tropics and subtropics. Currently, there is no licensed prophylactic or antiviral treatment for dengue. The novel DENV inhibitor JNJ-1802 can significantly reduce viral load in mice and non-human primates.

A quantitative systems pharmacology model for acute viral hepatitis B.

Hepatitis B liver infection is caused by hepatitis B virus (HBV) and represents a major global disease problem when it becomes chronic, as is the case for 80-90% of vertical or early life infections. However, in the vast majority (>95%) of adult exposures, the infected individuals are capable of mounting an effective immune response leading to infection resolution. A good understanding of HBV dynamics and the interaction between the virus and immune system during acute infection represents an essential step to characterize and understand the key biological processes involved in disease resolution, which may help to identify potential interventions to prevent chronic hepatitis B.

Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy.

This work explores the application of a physiologically structured population (PSP) framework in modeling hepatitis C virus (HCV) kinetics. To do so, a model was developed for the viral RNA load in plasma and liver as observed in 15 patients treated with a combination therapy of pegylated interferon, ribavirin, and telaprevir. By including both intracellular and extracellular processes of the HCV lifecycle, the model provided a description of the treatment effect on the intracellular HCV lifecycle.

Etravirine in treatment-experienced HIV-1-infected children 1 year to less than 6 years of age.

Objective: To describe the pharmacokinetics, safety, and efficacy of etravirine (ETR) in HIV-infected children 1 to less than 6 years of age.

Design: Phase I/II, open-label, multicenter, dose-finding study.

Methods: Antiretroviral therapy (ART)-experienced children in two age cohorts (I: 2 to <6 years; II: 1 to less than 2 years) received weight-based ETR, swallowed whole or dispersed in liquid, with optimized ART including a ritonavir-boosted protease inhibitor.

Immune network for viral hepatitis B: Topological representation.

The liver is a well-known immunotolerogenic environment, which provides the adequate setting for liver infectious pathogens persistence such as the hepatitis B virus (HBV). Consequently, HBV infection can derive in the development of chronic disease in a proportion of the patients. If this situation persists in time, chronic hepatitis B (CHB) would end in cirrhosis, hepatocellular carcinoma and eventually, the death of the patient.

A robust simulator for physiologically structured population models.

A framework to simulate physiologically structured population (PSP) models on high performance compute (HPC) infrastructure is built. Based on the model of a single cell, billions of cells can be simulated in an efficient way, allowing fast simulation of the interaction of an entire organ with other body parts. Trough combination of three state-of-the-art algorithms, the simulation time is decreased with multiple orders of magnitude.

Dynamic population pharmacokinetic-pharmacodynamic modelling and simulation supports similar efficacy in glycosylated haemoglobin response with once or twice-daily dosing of canagliflozin.

Aim: Canagliflozin is an SGLT2 inhibitor approved for the treatment of type-2 diabetes. A dynamic population pharmacokinetic-pharmacodynamic (PK/PD) model relating 24-h canagliflozin exposure profiles to effects on glycosylated haemoglobin was developed to compare the efficacy of once-daily and twice-daily dosing.

Methods: Data from two clinical studies, one with once-daily, and the other with twice-daily dosing of canagliflozin as add-on to metformin were used (n = 1347).

The method of averaging applied to pharmacokinetic/pharmacodynamic indirect response models.

The computational effort required to fit the pharmacodynamic (PD) part of a pharmacokinetic/pharmacodynamic (PK/PD) model can be considerable if the differential equations describing the model are solved numerically. This burden can be greatly reduced by applying the method of averaging (MAv) in the appropriate circumstances. The MAv gives an approximate solution, which is expected to be a good approximation when the PK profile is periodic (i.

Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies.

Purpose: Ibrutinib is an oral Bruton's tyrosine kinase inhibitor, recently approved for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) patients with at least one prior therapy. We developed a population pharmacokinetic (PK) model for ibrutinib in patients.

Methods: Ibrutinib PK data (3,477 observations/245 patients) were available from the following clinical studies: (1) A phase I dose-escalation study in recurrent B cell malignancies (dose levels of 1.