title: Drug absorption, distribution, metabolism and excretion considerations in critically ill adults.
abstract: BACKGROUND
  All critically ill patients require medication to treat organ dysfunction. However, the pharmacokinetics of drugs used to treat these patients is complex due to frequent alterations in drug absorption, distribution, metabolism, and excretion (ADME).
  
  
  METHODS
  This review examines pharmacokinetic aspects of drug administration for adult intensive care unit (ICU) patients. Specifically, the authors examine the ADME changes that occur and which should be considered by clinicians when delivering drug therapy to critically ill patients.
  
  
  CONCLUSIONS
  Dosage pharmacokinetics determined from single-dose or limited-duration administration studies in healthy volunteers may not apply to critically ill patients. Organ dysfunction among these patients may be due to pre-existing disease or the effects of a systemic or locoregional inflammatory response precipitated by their illness. Alterations in pharmacokinetics observed among the critically ill include altered bioavailability after enteral administration, increased volume of distribution and blood-brain barrier permeability and changes in P-glycoprotein and cytochrome P450 enzyme function. However, the effect of these changes on clinically important outcomes remains uncertain and poorly studied. Future investigations should examine not only pharmacokinetic changes among the critically ill, but also whether recognition of these changes and alterations in drug therapy directed as a consequence of their observation alters patient outcomes.
authors.affiliation: University of Calgary, Departments of Surgery and Community Health Sciences, Calgary, Alberta T2N 5A1, Canada.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Roberts
authors.forename: Richard I
authors.initials: RI
authors.lastname: Hall
mesh_terms: D000042:Absorption; D000328:Adult; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D016638:Critical Illness / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007362:Intensive Care Units; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics; D014947:Wounds and Injuries / Q000188:drug therapy / Q000473:pathology
chemical_list: D004364:Pharmaceutical Preparations