1. Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.
- Author
-
Logan R, Funk RS, Axcell E, and Krise JP
- Subjects
- Binding Sites drug effects, Cells, Cultured, Humans, Hydrogen-Ion Concentration, Lipids chemistry, Lysosomes chemistry, Pharmaceutical Preparations metabolism, Pharmacokinetics, Drug Interactions, Lysosomes drug effects
- Abstract
Introduction: Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered., Areas Covered: In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing., Expert Opinion: Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.
- Published
- 2012
- Full Text
- View/download PDF