Physiologically-based pharmacokinetic modelling of long-acting injectable cabotegravir and rilpivirine in pregnancy.

Aims: Long-acting cabotegravir and rilpivirine have been approved to manage HIV in adults, but data regarding safe use in pregnancy are limited. Physiologically-based pharmacokinetic (PBPK) modelling was used to simulate the approved dosing regimens in pregnancy and explore if C was maintained above cabotegravir and rilpivirine target concentrations (664 and 50 ng/mL, respectively).

Methods: An adult PBPK model was validated using clinical data of cabotegravir and rilpivirine in nonpregnant adults.

Evaluating Islatravir Administered Via Microneedle Array Patch for Long-Acting HIV Pre-exposure Prophylaxis Using Physiologically Based Pharmacokinetic Modelling.

Background And Objectives: Technologies for long-acting administration of antiretrovirals (ARVs) for the prevention and treatment of HIV are at the forefront of research initiatives aiming to tackle issues surrounding drug adherence with the current standard of once-daily oral administration. Islatravir (ISL) is an emerging ARV that shows promising characteristics for long-acting prevention and treatment both orally as well as through alternative routes of administration. Microneedle array patches (MAPs) are a pain-free and discreet transdermal delivery technology that offer extended-release administration of nanoparticulate drugs.

PBPK Modelling of Dexamethasone in Patients With COVID-19 and Liver Disease.

The aim of the study was to apply Physiologically-Based Pharmacokinetic (PBPK) modelling to predict the effect of liver disease (LD) on the pharmacokinetics (PK) of dexamethasone (DEX) in the treatment of COVID-19. A whole-body PBPK model was created to simulate 100 adult individuals aged 18-60 years. Physiological changes (e.

Drug-Drug Interactions in People Living With HIV at Risk of Hepatic and Renal Impairment: Current Status and Future Perspectives.

Despite the advancement of antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV), drug-drug interactions (DDIs) remain a relevant clinical issue for people living with HIV receiving ART. Antiretroviral (ARV) drugs can be victims and perpetrators of DDIs, and a detailed investigation during drug discovery and development is required to determine whether dose adjustments are necessary or coadministrations are contraindicated. Maintaining therapeutic ARV plasma concentrations is essential for successful ART, and changes resulting from potential DDIs could lead to toxicity, treatment failure, or the emergence of ARV-resistant HIV.

Predicting Drug-Drug Interactions between Rifampicin and Ritonavir-Boosted Atazanavir Using PBPK Modelling.

Objectives: The aim of this study was to simulate the drug-drug interaction (DDI) between ritonavir-boosted atazanavir (ATV/r) and rifampicin (RIF) using physiologically based pharmacokinetic (PBPK) modelling, and to predict suitable dose adjustments for ATV/r for the treatment of people living with HIV (PLWH) co-infected with tuberculosis.

Methods: A whole-body DDI PBPK model was designed using Simbiology 9.6.

The Current Landscape of Novel Formulations and the Role of Mathematical Modeling in Their Development.

Drug delivery is an integral part of the drug development process, influencing safety and efficacy of active pharmaceutical ingredients. The application of nanotechnology has enabled the discovery of novel formulations for numerous therapeutic purposes across multiple disease areas. However, evaluation of novel formulations in clinical scenarios is slow and hampered due to various ethical and logistical barriers.