What property leads to a high tissue partition coefficient (Kp)?

What property leads to a high tissue partition coefficient (Kp)?

• A. High tissue affinity
• B. High plasma protein binding
• C. Low lipophilicity
• D. Rapid renal clearance

Answer: (A)

High tissue affinity means the drug preferentially associates with tissue components, so it accumulates in tissues. At steady state, this leads to higher tissue concentrations relative to plasma, increasing the tissue-to-plasma partition coefficient (Kp). In other words, strong binding or partitioning into tissue stores more drug in the tissue compartment, raising Kp. Plasma protein binding tends to keep a portion of the drug bound in plasma and not available to distribute, so the free fraction that can reach tissues is reduced, which typically lowers Kp. Low lipophilicity reduces membrane passage and tissue partitioning, also lowering Kp. Rapid renal clearance reduces overall systemic exposure, limiting tissue distribution and decreasing Kp.

High tissue affinity means the drug preferentially associates with tissue components, so it accumulates in tissues. At steady state, this leads to higher tissue concentrations relative to plasma, increasing the tissue-to-plasma partition coefficient (Kp). In other words, strong binding or partitioning into tissue stores more drug in the tissue compartment, raising Kp.

Plasma protein binding tends to keep a portion of the drug bound in plasma and not available to distribute, so the free fraction that can reach tissues is reduced, which typically lowers Kp. Low lipophilicity reduces membrane passage and tissue partitioning, also lowering Kp. Rapid renal clearance reduces overall systemic exposure, limiting tissue distribution and decreasing Kp.