A drug exhibits nonlinear absorption due to saturable transport. How would this affect dose proportionality and what PK concept best describes it?

• A. Dose proportionality may be lost; AUC versus dose becomes nonlinear due to transporter saturation.
• B. Dose proportionality improves when a transporter saturates.
• C. AUC is always proportional to dose.
• D. Saturable transport has no effect on absorption PK.

Answer: (A)

Nonlinear absorption happens when the gut uses carrier-mediated transport with a limited capacity. As the dose goes up, those transporters begin to saturate, so the amount that can be absorbed does not keep increasing in step with the dose. That means the fraction absorbed (bioavailability) can drop at higher doses, and the relationship between dose and systemic exposure (AUC) is no longer a straight line.

The PK concept that best describes this is saturable absorption due to transporter capacity leading to nonlinear pharmacokinetics. So dose proportionality may be lost and AUC versus dose becomes nonlinear because absorption becomes rate-limited as transporters saturate. At low doses you might see approximate proportionality, but as the dose increases, the nonlinearity becomes apparent.