What PK considerations are relevant when dosing in obesity, and what modeling approach is commonly used to address them?

• A. Obesity primarily affects absorption; use compartmental models.
• B. Obesity alters Vd and clearance; allometric scaling and possibly separate body size descriptors or dedicated obesity PK models are used.
• C. Obesity has no effect on PK; use standard adult models.
• D. Obesity eliminates hepatic metabolism.

Answer: (B)

In dosing in obesity, the key idea is that body size and composition alter where a drug goes in the body (volume of distribution) and how quickly it is cleared. Because adipose tissue and lean mass change differently from total body weight, simply using standard adult parameters can misestimate exposure. The common approach to address this is allometric scaling, which relates PK parameters to body size with specific exponents (for example, clearance around 0.75 and volume around 1.0). In obesity, it’s often better to use size descriptors beyond total weight—such as fat-free mass, ideal body weight, or adjusted body weight—or to apply dedicated obesity PK models that account for differences in adipose versus lean tissue and possibly altered organ blood flow or function. This combination helps capture how obesity changes both Vd and clearance for many drugs.

Absorption is not the dominant factor in most PK changes seen with obesity, and assuming no effect on PK altogether or that hepatic metabolism is eliminated is not accurate.