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About this research group
The research group investigates the pharmacology of existing and new drugs for tuberculosis, using a translational approach that extends from molecular pharmacology to clinical pharmacology studies and to clinical trials, supported by advanced laboratory and modeling techniques.
Aims
The aim of the research group Pharmacology of anti-tuberculosis drugs is to optimize the treatment of tuberculosis (TB), the leading infectious disease killer worldwide.- The central concept in this research line is that the efficacy and toxicity of anti-TB drugs is determined by the systemic or local concentrations of these drugs.
- The research group is developing a comprehensive, application-oriented translational pharmacological research line.
- The translational approach adopted by the research group requires expertise in a broad field of pharmacological techniques.
- The research group is intensively collaborating with other TB researchers and research groups within Radboudumc and around the globe.
Aims
The aim of the research group Pharmacology of anti-tuberculosis drugs is to optimize the treatment of tuberculosis (TB), the leading infectious disease killer worldwide.- The central concept in this research line is that the efficacy and toxicity of anti-TB drugs is determined by the systemic or local concentrations of these drugs. This means that the dose of a drug (combination) needs to be assessed based on the relationship between the dose administered and the concentrations achieved (pharmacokinetics) and the relationship between concentrations and effect (pharmacodynamics).
- The research group is developing a comprehensive, application-oriented translational pharmacological research line. This research line reaches from preclinical (molecular) pharmacological TB research (in collaboration with the Department of Pharmacology and Toxicology) to clinical pharmacology studies in small patient groups (adherence, pharmacokinetic, dose finding and drug-drug interaction studies) to pharmacokinetic/dynamic studies embedded in clinical trials. The research group is focusing on existing and new anti-TB drugs and their application in both adults and children.
- The translational approach adopted by the research group requires expertise in a broad field of pharmacological techniques, extending from in vitro transport-assays, ‘state of the art’ assays for drugs in various matrices, to advanced pharmacokinetic data analysis techniques. The research group is supported by the pharmacokinetic laboratory and the Radboud Applied Pharmacometrics group based in the Department of Pharmacy.
- The research group is intensively collaborating with other TB researchers and research groups within Radboudumc and around the globe, and helps to develop pharmacological research capacity in resource-poor countries where TB is endemic.
Discoveries
Multiple discoveries are listed below.- Adherence to TB drugs, essential to an adequate response, can be measured with combinations of conventional and more sophisticated methods.
- The pharmacokinetics of all first-line TB drugs was described in many populations across the world, as a starting point for treatment optimization.
Discoveries
Multiple discoveries are listed below.- Adherence to TB drugs, essential to an adequate response, can be measured with combinations of conventional and more sophisticated methods.
- The pharmacokinetics of all first-line TB drugs was described in many populations across the world, as a starting point for treatment optimization.
- Some TB drugs should be administered in a higher dose in case of diabetes mellitus, a common co-morbidity with TB.
- Most TB drugs do not affect the disposition of the pivotal anti-diabetic metformin in vitro; in vivo metformin can be combined with the TB drug rifampicin without changes in dose.
- Rifampicin and clofazimine, but no other TB drugs, inhibit the most relevant (ABC) transporters of other drugs.
- The effect of rifampicin on the antiretroviral drugs lopinavir/ritonavir and efavirenz and the anti-TB drug moxifloxacin was assessed, yielding information about optimal dosing of these drugs in combination.
- Various optimal sampling strategies and modelling approaches were developed to personalize dosing of TB drugs (Therapeutic Drug Monitoring).
- High dose rifampicin can be used to optimize treatment of pulmonary, as evidenced by a series of studies in Indonesia and Africa.
- High dose rifampicin can decrease the mortality of tuberculous meningitis, the most severe form of TB, as evidenced by a series of studies in Indonesia.
