Drug absorption, distribution, metabolism and excretion considerations in critically ill adults

Introduction: 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). Areas covered: 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. Expert opinion: 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.