title: Introduction to drug pharmacokinetics in the critically ill patient.
abstract: Despite regular use of drugs for critically ill patients, overall data are limited regarding the impact of critical illness on pharmacokinetics (PK). Designing safe and effective drug regimens for patients with critical illness requires an understanding of PK. This article reviews general principles of PK, including absorption, distribution, metabolism, and elimination, and how critical illness can influence these parameters. In the area of drug absorption, we discuss the impact of vasopressor use, delayed gastric emptying and feeding tubes, and nutrient interactions. On the topic of drug distribution, we review fluid resuscitation, alterations in plasma protein binding, and tissue perfusion. With drug metabolism, we discuss hepatic enzyme activity, protein binding, and hepatic blood flow. Finally, we review drug elimination in the critically ill patient and discuss the impact of augmented renal clearance and acute kidney injury on drug therapies. In each section, we highlight select literature reviewing the PK impact of these conditions on a drug PK profile and, where appropriate, provide general suggestions for clinicians on how to modify drug regimens to manage PK challenges.
authors.affiliation: UMass Memorial Medical Center, Worcester, MA. Electronic address: Brian.Smith4@umassmemorial.org.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Smith
authors.affiliation: UMass Memorial Medical Center, Worcester, MA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Yogaratnam
authors.affiliation: Northwestern Memorial Hospital, Chicago, IL.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Levasseur-Franklin
authors.affiliation: Brigham and Women's Hospital, Boston, MA.
authors.forename: Allison
authors.initials: A
authors.lastname: Forni
authors.affiliation: UMass Memorial Medical Center, Worcester, MA; Massachusetts College of Pharmacy and Health Sciences, Worcester, MA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fong
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology; D001682:Biological Availability; D003422:Critical Care / Q000379:methods; D016638:Critical Illness; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D008099:Liver / Q000503:physiopathology; D008657:Metabolic Clearance Rate / Q000502:physiology; D010599:Pharmacokinetics; D011485:Protein Binding / Q000502:physiology