Significant achievements in pharmacology 2009-2014
Automated solid-phase extraction and liquid handler system (left) and high-throughput liquid chromatography coupled with tandem mass spectrometry (right)
- Demonstrated that young children with severe malaria are under-dosed with the currently recommended parenteral artesunate treatment (Figure 4). A pharmacometric modelling approach was used to suggest a revised dose regimen for these children, a regimen that was endorsed by the working committee for the 3rd edition of the WHO Guidelines for the Treatment of Malaria
- Demonstrated that young children with uncomplicated malaria are under-dosed with the currently recommended dihydroartemisinin-piperaquine treatment. A similar pharmacometric modeling approach to that for severe malaria was used and again our revised dosing regimen was adopted by WHO. We have also shown that chloroquine and lumefantrine are under-dosed in young children with uncomplicated malaria.
- Used pharmacometric approaches to investigate the drug-exposure of antimalarial treatments in pregnant women with uncomplicated malaria treated with artesunate, artemether, dihydroartemisinin, piperaquine, lumefantrine, mefloquine, amodiaquine, and quinine. More work is needed to evaluate the clinical implications and to suggest revised dose regimens.
- The pharmacokinetic and pharmacodynamic properties of artesunate and its main metabolite dihydroartemisinin were evaluated in populations with different proportions of artemisinin-resistant falciparum malaria in Myanmar, Thailand and Cambodia: this is the first crucial step in understanding the mechanism of action in drug-resistant parasites and suggesting evidence-based dose recommendations for these populations.
- Substantial pharmacokinetic drug-drug interactions were demonstrated between primaquine/chloroquine, artemether/efavirenz, lumefantrine/efavirenz, artemether/nevirapine, artesunate/nevirapine, artemether/lopinavir-ritonavir, lumefantrine/lopinavir-ritonavir, oseltamivir/zanamivir, artemether/rifampicin, lumefantrine/rifampicin, as was an absence of interaction between piperaquine and food.
- Developed and validated new pharmacometric techniques to investigate the pharmacokinetic and pharmacodynamic properties of antimalarial drugs through the implementation of mechanistically accurate parasite models and time-to-event modelling of vivax and falciparum malaria.
- Developed a framework for optimal design of antimalarial pharmacokinetic and pharmacodynamic clinical studies and designed a novel methodology for pharmacometric-based power calculations.
- Defined the pharmacokinetics, efficacy and safety of anti-influenza drugs oseltamivir and zanamivir in healthy volunteers, in the obese, as prophylaxis, in combination with other antivirals, and in severe influenza.
- Development and validation of bioanalytical methods to quantify and detect drugs using dried blood spot methodologies to facilitate pharmacokinetic field studies. Dried blood spot assays have been developed for the quantification/detection of tafenoquine, quinine, mefloquine, sulfadoxine, pyrimethamine, lumefantrine, chloroquine and its metabolite desethylchloroquine.
- Development, validation and use in PK studies of bioanalytical methodologies to quantify drugs in patient whole blood and/or plasma to enable accurate pharmacokinetic evaluations. Methods have been developed and validated for tafenoquine, zanamivir, artemether, dihydroartemisinin, and artemisinin in plasma and for artesunate, dihydroartemisinin, and artemisinin in whole blood.