Pharmacokinetics/Pharmacodynamics

Learning Objectives

Describe the changes in critically ill patients that

alter drug absorption.

Depict the effects of changing hepatic blood flow,

intrinsic activity, and protein binding on drug

metabolism.

Differentiate between different critically ill patient

populations and the expected pharmacokinetic (PK)

changes.

Identify the desired pharmacodynamic variables

associated with efficacy in select drugs.

α1-Acid glycoprotein

AKI

Acute kidney injury

ARC

Augmented renal clearance

AUC

Area under the curve

AUC/MIC

Ratio of area under the curve to the

minimum inhibitory concentration for

the bacterial pathogen

hours to the minimum inhibitory

concentration for the bacterial pathogen

CKD

Chronic kidney disease

Cmax/MIC

Ratio between the maximum drug

concentration and the minimum

inhibitory concentration for the bacterial

pathogen

fT>MIC

Free drug concentration time above the

minimum inhibitory concentration for

the bacterial pathogen

ECMO

Extracorporeal membrane oxygenation

GFR

Glomerular filtration rate

ICU

Intensive care unit

MIC

Minimum inhibitory concentration

PD

Pharmacodynamic(s)

PK

Pharmacokinetic(s)

TBI

Traumatic brain injury

TDM

Therapeutic drug monitoring

Vd

Volume of distribution

Self-Assessment Questions

Answers and explanations to these questions can be

found at the end of this chapter.

J.H. is a 30-year-old man admitted to the inten-

sive care unit (ICU) for septic shock. He initially

received 30 mL/kg of normal saline for intravenous

fluid resuscitation. He required further fluid admin-

istration to improve his pulse pressure variation.

Despite prophylaxis with enoxaparin 30 mg subcu-

taneously every 12 hours, J.H. has a proximal deep

venous thrombosis. Which pharmacokinetic (PK)

alteration most likely contributed to this therapeutic

failure?

secondary to decreased volume of distribution

(Vd).

decreased absorption.

anti-Xa

activity

secondary

to

decreased hepatic metabolism.

anti-Xa

activity

secondary

to

decreased renal elimination.

Questions 2–4 pertain to the following case.

E.W. is a 48-year-old man (height 70 inches, weight 85

kg) admitted to the trauma ICU after a motorcycle col-

lision. E.W. presents with a traumatic brain injury (TBI;

head computed tomography [CT] reveals a depressed

skull fracture, frontal subarachnoid hemorrhage, and

right intraparenchymal hemorrhage), right acetabulum

fracture, bilateral rib fractures, and abdominal trauma.

According to his abdominal CT, E.W. must go to the

operating room for an exploratory laparotomy for repair

of several serosal tears. After surgery, E.W. requires sig-

nificant resuscitation in his first 24 hours of admission

(5 L of normal saline). He is made NPO to allow bowel

rest.

E.W.’s laboratory values are as follows: serum cre-

atinine (SCr) 1.1 mg/dL, blood urea nitrogen (BUN) 17

mg/dL, and white blood cell count (WBC) 19 × 103 cells/

mm3. The patient’s pulmonary artery catheterization val-

ues are cardiac index 4.2 L/minute/m2 (normal 2.8–3.6

L/minute/m2) and pulmonary artery wedge pressure

16 mm Hg. His medication therapy includes a fentanyl

continuous infusion of 75 mcg/hour, a propofol con-

tinuous infusion of 15 mcg/kg/minute, pantoprazole 40

mg intravenously every 24 hours, enoxaparin 30 mg