Final answer:
The third barrier a drug must pass to reach its target organ is the blood-brain barrier (BBB), particularly for drugs targeting the central nervous system.
Step-by-step explanation:
The third barrier a drug must pass to get to its target organ, after crossing cellular membranes and avoiding efflux transporters and metabolic enzymes in the gastrointestinal (GI) tract, is the blood-brain barrier (BBB). This is especially relevant for drugs intended to affect the central nervous system (CNS). The BBB functions to protect the brain from potentially harmful substances in the blood, but this also makes it challenging to deliver drugs to the CNS. Drugs that are able to cross the BBB typically have certain physicochemical properties, such as a small polar surface area, and may also require specific design strategies to minimize efflux by transporters like P-glycoprotein (PgP).