Which in vitro system is used to measure liver intrinsic clearance (CLint)?

• A. Renal tubule cells.
• B. Liver microsomes or hepatocytes.
• C. Intestinal mucosa cells.
• D. Brain endothelial cells.

Answer: (B)

Intrinsic clearance is the liver’s enzymatic capacity to metabolize a drug, independent of blood flow and binding. To quantify this in vitro, you use liver-derived systems that contain the metabolic enzymes. Liver microsomes provide the enzymes located in the endoplasmic reticulum, mainly cytochrome P450s, suitable for assessing hepatic phase I metabolism. Hepatocytes are intact liver cells that carry both phase I and phase II enzymes and cofactors, offering a more physiologic view of hepatic metabolism. By incubating the drug with either system and measuring the rate of drug disappearance (often with appropriate cofactors like NADPH for microsomes), you derive intrinsic clearance per unit of protein or per number of cells.

Other tissues listed do not measure hepatic intrinsic clearance because they reflect metabolism characteristic of those specific tissues (renal tubule cells for kidney metabolism, intestinal mucosa for gut metabolism, brain endothelial cells for the blood–brain barrier).