Which factor would most likely slow tissue distribution?

Which factor would most likely slow tissue distribution?

• A. Increased perfusion.
• B. Increased tissue membrane permeability.
• C. Increased plasma protein binding.
• D. Smaller pH differences between compartments.

Answer: (C)

The amount of drug that can distribute into tissues is governed by the fraction that is free in plasma. Only the unbound portion can diffuse across capillary walls and enter tissues; the portion bound to plasma proteins like albumin remains in the blood and is not readily available for distribution. So, when plasma protein binding increases, the free fraction decreases, giving a slower rate and reduced extent of tissue distribution. This is reflected in a smaller apparent volume of distribution and slower equilibration between plasma and tissues. While higher perfusion and greater membrane permeability generally speed distribution, and pH differences can influence ion trapping, the direct effect that most slows distribution is increased plasma protein binding.

The amount of drug that can distribute into tissues is governed by the fraction that is free in plasma. Only the unbound portion can diffuse across capillary walls and enter tissues; the portion bound to plasma proteins like albumin remains in the blood and is not readily available for distribution. So, when plasma protein binding increases, the free fraction decreases, giving a slower rate and reduced extent of tissue distribution. This is reflected in a smaller apparent volume of distribution and slower equilibration between plasma and tissues. While higher perfusion and greater membrane permeability generally speed distribution, and pH differences can influence ion trapping, the direct effect that most slows distribution is increased plasma protein binding.