title: Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The University of Kansas, Department of Pharmaceutical Chemistry, 2095 Constant Ave., Lawrence, KS 66047, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Logan
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Funk
authors.forename: Erick
authors.initials: E
authors.lastname: Axcell
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krise
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D008247:Lysosomes / Q000737:chemistry / Q000187:drug effects*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics
chemical_list: D008055:Lipids; D004364:Pharmaceutical Preparations