Method development studies

Through an extensive pharmacological development work, we have successfully developed and validated a new method for measuring the concentration of atorvastatin and all primary metabolites directly in blood with modern mass spectrometric methodology. We have shown, for the first time, that the sum of parent drug and metabolites was stable at room temperature over several days. Our efficient analysis process and promising pilot results indicate that this method can effectively measure statin levels in clinical settings, such as in a doctor’s office or hospital follow-up appointments. Similar advancements have been made for simvastatin analysis, expanding the scope of our research.

In order to study adherence with statin therapy with the new method, we conducted a pharmacokinetic study STAT-MON 1 involving 48 coronary patients to assess complience with statin treatment. By establishing clinical decision limits based on dose-normalized cut‐off values for statin concentrations and an algorithm for adherence, we were able to discriminate patients with high compliance, those with reduced adherence, and those who are not taking the medication at all (providing valuable insights into patient behavior and treatment efficacy). The methodology used to establish these compliance limits could be applicable to other medications as well.

Our latest study, STAT-MON 2, conducted in the spring of 2021 with 60 patients, aims to validate and further refine the decision limits established in STAT-MON 1.

Personalized Statin Monitoring (”STAT-MON”) 2 Study: Validation of cut-off values to discriminate among adherence, partial adherence and nonadherence to atorvastatin therapy determined by parent drug and metabolites in blood samples

The purpose of the study is to validate our newly developed decision thresholds (cut-offs) for classifying patients with normal and reduced adherence to atorvastatin using a new direct method. A pharmacokinetic study will include 60 patients using atorvastatin at doses of 20 mg, 40 mg, and 60 mg. All patients have high adherence at the start of the study. They will then stop taking their statin and come for blood sampling on the following 4 days. Statin levels measured in the blood each day will be validated against the decision thresholds developed in the first study. The project itself will not provide new knowledge about health or disease, but the decision thresholds generated will be used in later randomized studies.

Project Leader: John Munkhaugen

Study Period: 2021-2028