Interindividual variability in statin pharmacokinetics and effects of drug transporters.

Abstract

Statins are HMG-CoA reductase inhibitors that primarily lower plasma cholesterol levels. It has been suggested that the myotoxic response is a direct result of hydroxymethylglutaryl-CoA reductase inhibition and dose-dependent. Therefore, an accurate understanding of the combination of drugs that inhibit statin metabolism and factors that cause interindividual variability in the pharmacokinetics of statin is important to avoid serious side effects of statins. Relevant articles included in this review were identified through a PubMed search (through May 2023). This review provides an overview of hepatic and intestinal metabolism of statins, followed by a discussion of drug-drug interactions and interindividual variables that influence statin pharmacokinetics: gut bacteria, disease, and pharmacokinetics-related genetic polymorphisms. Drug-drug interactions have a strong influence on statin pharmacokinetics, and gut microbiota, disease, and genetic polymorphisms all contribute significantly to interindividual variation in statin pharmacokinetics. Individual optimization of statin treatment requires studies that consider the progression of the disease and associated changes in concomitant medications.