title: Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol.
abstract: BACKGROUND
  A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life.
  
  
  METHODS
  This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination. Specific considerations are also given for three commonly prescribed drugs in palliative care: morphine, midazolam and haloperidol).
  
  
  CONCLUSIONS
  The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines. Until then knowledge of pharmacokinetics and the physiological changes that occur in the final days of life can provide a base for dosing adjustments that will improve the quality of life of terminally ill patients. As the interaction of drugs with the physiology of dying is complex, pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.
authors.affiliation: a Department of Hospital Pharmacy , Erasmus Medical Centre , Rotterdam , the Netherlands.
authors.forename: L G
authors.initials: LG
authors.lastname: Franken
authors.affiliation: a Department of Hospital Pharmacy , Erasmus Medical Centre , Rotterdam , the Netherlands.
authors.forename: B C M
authors.initials: BC
authors.lastname: de Winter
authors.affiliation: b Palliative Care Centre , Laurens Cadenza , Rotterdam , the Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: van Esch
authors.affiliation: c Department of Medical Oncology , Erasmus MC Cancer Institute , Rotterdam , the Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: van Zuylen
authors.affiliation: b Palliative Care Centre , Laurens Cadenza , Rotterdam , the Netherlands.
authors.forename: F P M
authors.initials: FP
authors.lastname: Baar
authors.affiliation: d Intensive Care, Department of Paediatric Surgery , Erasmus MC-Sophia Children's Hospital , Rotterdam , the Netherlands.|e Pain Expertise Centre , Erasmus MC-Sophia Children's Hospital , Rotterdam , the Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Tibboel
authors.affiliation: f Hospital Pharmacy - Clinical Pharmacology , Academic Medical Centre , Amsterdam , the Netherlands.
authors.forename: R A A
authors.initials: RA
authors.lastname: Mathôt
authors.affiliation: a Department of Hospital Pharmacy , Erasmus Medical Centre , Rotterdam , the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van Gelder
authors.affiliation: a Department of Hospital Pharmacy , Erasmus Medical Centre , Rotterdam , the Netherlands.
authors.forename: B C P
authors.initials: BC
authors.lastname: Koch
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D006220:Haloperidol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics; D008874:Midazolam / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009020:Morphine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010166:Palliative Care / Q000379:methods*; D011788:Quality of Life; D013727:Terminal Care / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives; D009020:Morphine; D006220:Haloperidol; D008874:Midazolam
keywords: Haloperidol; midazolam; morphine; palliative care; pharmacokinetics; terminal illness