Research Group Toxicology and Energy Metabolism

Prof. Dr. Stephan Krähenbühl

Toxicology

Our group mainly focuses on the toxicity of drugs on the liver, skeletal muscle and/or bone marrow. Special emphasis is placed on the mechanisms of cell death induction, in particular apoptosis and necrosis. In recent projects, we have investigated the toxicity of amiodarone on hepatocytes and pneumocytes, the toxicity of statins on skeletal muscle and of benzbromarone on hepatocytes. Current projects include the toxicity of clopidogrel and ticlopidine on hepatocytes and on myelocytes, the molecular mechanisms of toxicity of statins on skeletal muscle and other cells and the cellular toxicity of amiodarone and amiodarone derivatives on liver and lung in relation to its effects on hERG channels.
Furthermore, we study the effect of drugs on the activity of the carnitine carrier OCTN2. Such interactions can lead to secondary carnitine deficiency, which can be associated with myopathy and encephalopathy.

Energy metabolism

A special field of interest of our group is mitochondrial function and metabolism, in particular concerning carnitine. Carnitine is a small molecule, which is needed for transport of long-chain fatty acids into the mitochondrial matrix. We have developed a sensitive LC/MS-method for the determination of carnitine and acylcarnitines. Current projects include carnitine homeostasis in vegetarians, and the physiology and pharmacology of carnitine in the elderly. Furthermore, we are interested in carnitine deficiency states, e.g. associated with drug use or with hemodialysis, and in the regulation of OCTN2, the carnitine carrier.

Clinical Studies

The division of clinical pharmacology & toxicology runs the clinical research centre (CRC) which is located in the University Hospital of Basel and which is suitable for conducting phase I and early phase II studies. Our special fields of interest include studies in the areas of drug-drug interactions, pharmacokinetics/pharmacodynamics and dose adaptation in patients with renal or liver failure.

Practical drug therapy

Our interests in drug therapy include dose adaptation in patients with liver and/or kidney disease, pharmacotherapy in the elderly and the detection and clinical management of drug-drug interactions. Our Division runs a regional centre for adverse drug events. Adverse drug events are reported from the University Hospital of Basel or from other hospitals or practitioners, are elaborated and finally transmitted to the Swiss Pharmacovigilance Centre at Swissmedic in Berne.