Insights on Volume of Distribution of Acids.

Acidic drugs generally have small steady-state volumes of distribution () around 0.1-0.25 L/kg, due to high binding to serum albumin and low binding to phospholipids in tissues. Acids can reach pharmacological targets in tissues despite small . Enterohepatic recirculation (EHR) of parent drug or reversible acyl glucuronide can increase the of acids. However, rational design to incorporate EHR as a mechanism to increase remains challenging because of the complexity of EHR and lack of reliable predictive tools. Uptake transporters can increase the of acidic drugs by increasing the liver drug concentration and can facilitate EHR through enhancing biliary elimination and glucuronide formation. Half-life extension of acids mainly relies on reducing clearance or using modified release formulations rather than modulating .