RX523 Pharmacokinetics in Patients with Obesity

What increases with obesity?

- Lean body and adipose mass

- Plasma lipids and blood volume

- Extracellular fluid volume

- Fatty infiltration to liver

- Organ hypertrophy

- Alpha-1 acid glycoprotein

Lean body mass/weight (LBW)

Combination of body cell mass, extracellular water, and non-fat connective tissue

Fat-free mass (FFM)

Muscle, bone, vital organs, and extracellular fluid. Clinically interchangeable with LBW for drug dosing calculations.

Ideal body weight (IBW)

Historical studies of adult weight and height that compared to relative mortality of different weight-height combinations. Often used as a surrogate for LBW.

Adjusted body weight (AdjBW)

Weight calculated and used for drug dosing in clinical settings when the IBW is thought to underestimate and the TBW to overestimate drug distribution.

Body mass index (BMI)

Measurement of the TBW in kilograms divided by the square of the height in meters. Used in the classification of obesity.

How does total body weight change in obesity?

- Percent of lean tissue per kg of TBW is reduced

- Percent of fat tissue per kg of TBW is doubled

What are the key points of absorption in obesity?

- Potentially accelerated gastric emptying

- Altered enterohepatic cycling

- Rate and extent is similar to non-obese patients

What are the key points of distribution in obesity?

- Ratio ≥ 1, use TBW

- Ratio < 1, use IBW or AdjBW

What are the protein binding considerations in obesity?

- Drugs that bind to albumin show no change

- Alpha-1 glycoprotein may be altered

- Elevated lipoprotein concentrations

What are the metabolism considerations in obesity?

- Decreased CYP3A4 activity

- Increased CYP2E1 activity

- Increased glucuronidation and sulfation

What are the absorption changes in obesity?

- Accelerated gastric emptying

- Increased gut perfusion

- Increased subcutaneous fat

What are the distribution changes in obesity?

- Increased CO and regional blood flow

- Increased AAG and plasma lipoproteins

- Altered Vd

What are the elimination changes in obesity?

- Fatty infiltration to the liver

- Altered renal and hepatic clearance

Which of the following is predicted to increase in patients with obesity?

Extracellular fluid volume and lean body mass

Which statement describes the appropriate method for estimating renal function in patients with obesity?

Use the Cockcroft-Gault equation and include the patient's adjusted body weight (AdjBW).

Which statement accurately describes predicted alterations to protein binding in patients with obesity?

The fu of weak bases will decrease due to increased alpha-1 acid glycoprotein.

The Vd will always increase proportionally to increased weight for highly lipophilic drugs.

False

31 kg/m2

Class 1

37 kg/m2

Class 2

45 kg/m2

Class 3