Which strategies could improve effective exposure for a drug with poor absorption (low oral bioavailability)?

• A. Decrease dose
• B. Ignore
• C. Formulation changes, alternative routes, or dosing modifications
• D. Increase dose

Answer: (C)

When oral bioavailability is poor, the aim is to increase how much drug reaches the bloodstream or to bypass the absorption barriers in the gut. This can be done by changing the formulation to improve solubility, dissolution, or permeability, such as using more soluble salt forms, particle size reduction, solid dispersions, or absorption enhancers. Another route is to administer the drug by a different pathway that avoids the gut (for example, intravenous, sublingual, transdermal, or inhaled delivery), which can achieve higher and more predictable exposure. Dosing modifications, like using a loading dose or adjusting the dosing interval to optimize exposure, can also help when the goal is to reach effective levels more reliably. In contrast, simply decreasing the dose reduces exposure, and ignoring the absorption issue won’t improve it.