Final answer:
The fourth barrier a drug must pass is the plasma protein binding (PPB) barrier. High protein binding limits free drug concentration in the bloodstream, while lower binding increases availability for tissue absorption. Overcoming the BBB is crucial for CNS-targeted drugs.
Step-by-step explanation:
The fourth barrier that a drug must pass to get to its target organ is the plasma protein binding (PPB) barrier. In the bloodstream, drugs encounter various hurdles that can affect their ability to reach their target tissues and organs. One key factor is the drug's affinity for plasma proteins. High plasma protein binding can restrict the amount of free, unbound drug available to penetrate tissues and can lead to a reduced pharmacological effect. Conversely, drugs with a lower affinity for plasma proteins have more unbound drug available to interact with the target organ. Furthermore, drugs intended to treat conditions in the central nervous system must overcome the blood-brain barrier (BBB), which is highly selective and restricts the passage of many compounds from the bloodstream into the brain. Pharmaceutical companies invest significant research efforts into developing drugs with properties that allow them to cross the BBB effectively.