ATP-binding cassette (ABC) drug transporters ABCB1 [P-glycoprotein (Pgp)] and ABCG2 are expressed in many tissues including those of the intestines, the liver, the kidney and the brain and are known to influence the pharmacokinetics and toxicity of therapeutic drugs. In vitro studies involving their functional characteristics provide important information that allows improvements in drug delive...

Dolutegravir is neither an inducer nor inhibitor of metabolising enzymes, and it therefore has a low propensity to act as perpetrator drug-drug interactions. Clinically significant decreases in dolutegravir exposure occur when co-administered with strong inducers (e.g. rifampicin, efavirenz) drug enzymes efflux transporters for which substrate – this can be overcome by increasing the dose from ...

Pharmacokinetic interactions, e.g. modulation of drug transporters like P-glycoprotein at the blood-brain barrier, can be a reason for treatment non-response. This study focuses on the influence of induction of drug transporters on the disposition of the antipsychotic drugs risperidone and 9-hydroxyrisperidone. Brain and serum concentrations of risperidone and its active metabolite 9-hydroxyris...

Similar drug molecules often have similar properties and activities. Therefore, quantifying molecular similarity is central to discovery optimization. Here I review computational methods using measures developed in my group within the interdisciplinary network NCCR TransCure investigating physiology, structural biology pharmacology of ion channels membrane transporters. We designed a 3D shape p...

The liver mainly regulates the ADME (absorption, distribution, metabolism and excretion) properties of numerous endogenous and exogenous compounds with metabolic enzymes such as chytochrome P450 (CYP) and membrane transporters such as organic anion transporting polypeptides (OATPs) and organic cation transporters (OCTs). Recently, clinical studies investigating drug-drug interactions (DDIs) or ...

The most important causes of treatment failure in canine lymphoma include intrinsic or acquired drug resistance. Thus, elucidation of molecular mechanisms of drug resistance is essential for the establishment of better treatment alternatives for lymphoma patients. The overexpression of drug transporters is one of the most intensively studied mechanisms of drug resistance in many tumors. In cani...