The Project Laboratory experiments produced data on the effects of drug-metabolizing enzymes and drug-transporting proteins on statins, and, additionally, on the pharmacological and toxicological effects of statins. For the first time, comparable data for all statins have been attained, and the experiments resulted in novel findings. The laboratory experiments provided essential data for the systems pharmacology algorithm. In addition, the Project included an observational clinical study that recruited patients who initiated a statin treatment for the first time. The patients were followed up for a one-year period. The data from this study is utilized for modelling purposes in the algorithm. A biobank study was included to the Project to study the effects of genetic variants on statin treatment outcome in a real-world setting. This biobank study investigated, e.g. the roles of certain genetic variants in statin intolerance, and found associations between genetic variants and intolerance to simvastatin and pravastatin. A physiologically based core model has been developed for all statins, consisting of interlinked physiological compartments, allowing the drug to be absorbed and move in the blood circulation to the various organs. The model accounts for metabolism and active transport in the gut and liver, and their changes due to drug-drug interactions and genetic variants. The intracellular liver compartments and the muscle compartment, and the established concentration-response relationships are used to estimate cholesterol-lowering efficacy and risk of muscle toxicity. Several articles, which cover widely the Project results, have already been published and several are currently being prepared for publication.
