Future vision Clinical Pharmacology
Highly integrated within MORU Tropical Health Network activities across the globe, Clinical Pharmacology Department’s strengths are in scientific output, our laboratories and access to clinical trials and samples
We anticipate working in new trials and disease areas including TB, Hepatitits C and filariasais, medicine quality and pharmacology based basic science (omics). Specifically, Clinical Pharmacology plans to work on:
Antimalarial dose optimisation | Treatment of multi-drug resistant malaria | Malnutrition and malaria treatment | Pharmacokinetic and pharmacodynamic properties of Hepatitis C agents | Pharmacokinetic and pharmacodynamic properties of anti-infective agents | Physiologically based pharmacokinetic (PBPK) modelling | Medicine Quality | Improved diagnostic tools for neglected tropical diseases
We will continue to optimise antimalarial dose regimens in young children and pregnant women. Drug exposure does not commonly scale linearly with body weight, and small children often need a higher dosage (mg/kg) compared to adults to achieve equivalent exposures. Drug exposure is often different in pregnant women compared to non-pregnant adults due to physiological alterations during pregnancy. Individual clinical trial analyses and large-scale meta-analysis on the pharmacokinetic properties of antimalarial drugs will be conducted and reported.
Several projects are on-going investigating efficacy, safety, and potential drug-drug interactions of antimalarial drugs when used in novel combination treatments. Particular focus will be on triple combination therapy with or without other transmission and/or vector control agents such as primaquine and/or ivermectin. Pharmacokinetic and pharmacodynamic modelling of these combinations aims to inform treatment policy of multi-drug resistant malaria and provide treatment options in malarial elimination campaigns.
We will continue to evaluate the pharmacokinetic and pharmacodynamic properties of antimalarial drugs in malnourished children, and use modelling and simulation to suggest revised dose regimens. The collaboration with the MSF-site in Niger will continue to gather data in this particularly vulnerable group of patients.
Two clinical trials are on-going in Vietnam and Myanmar, investigating the efficacy and safety of sofosbuvir and daclatasvir in the treatment of Hepatitis C. Bioanalytical assays will be developed to quantify these drugs in biological fluids, such as plasma and whole blood. Pharmacokinetic and pharmacodynamic samples will be collected in these studies so that the pharmacokinetic properties can be evaluated, and linked to their pharmacodynamic effect (viral elimination).
A collaboration between MORU and DNDi is ongoing to provide pharmacokinetic and pharmacodynamic modelling support to inform the development of novel drugs for neglected tropical diseases (e.g. leishmaniasis, Chagas disease and filariasis). The initial focus will be on filariasis with the aim to provide a rational modelling framework for in-vitro to in-vivo scaling, animal to human scaling, healthy volunteer to patient scaling, and to perform phase I-IV clinical trial evaluation of novel drugs under development.
We will initiate more projects using a PBPK methodology. These analyses will be carried out using the software SimCYP, which has been developed specifically for PBPK modelling. Initially, we will investigate the impact of pregnancy on the pharmacokinetics of piperaquine by utilizing the built-in pregnancy module in SimCYP and compare to clinical data available at the department.
The department aim to establish research in medicine quality, in order to determine the amount of active drug content (API) present in marketed products and medicine used in clinical trials. We also aim at evaluating the abilities of handheld analytical devices alone, or in combination, to detect substandard and falsified medicine. Assessing whether handheld devices can accurately quantify drug content of medicine or detect medicine with reduced API using adapted chemometrics is a key objective of that work.
The challenge for the management of tropical diseases is often not the treatment, but the diagnosis. Patients report to hospitals with nonspecific symptoms, which can have various origins. Although the symptoms are similar, treatment differs between pathogens. Conventionally used diagnostic tools like serology and/or microscopy may deliver reliable results but are often only possible in later stages of the infection. Time-consuming cultures of the pathogen and sophisticated equipment may be required to deliver a clear identification. Using a proteomics approach, we aim to identify novel diagnostic markers for neglected tropical diseases like melioidosis, scrub typhus and rabies. Such biomarkers could be used to develop non-invasive, field-based rapid tests, allowing for early and reliable identification of pathogens in patients.