Final answer:
The first barrier a drug must pass to get to its target organ is absorption through the cellular membrane in the GI tract, typically through passive diffusion. In the bloodstream, drugs encounter additional barriers like enzymatic hydrolysis, plasma protein binding, and for CNS drugs, the blood-brain barrier.
Step-by-step explanation:
The first barrier a drug must pass to get to its target organ is the absorption through the cellular membrane in the gastrointestinal (GI) tract. The most common mechanism by which drugs cross this barrier is passive diffusion, which accounts for the absorption of approximately 95% of all commercial drugs. However, drugs face several barriers to exposure, including cell membranes, metabolic enzymes, efflux transporters, and binding proteins. Compounds need to overcome these barriers in order to maximize their oral absorption and therapeutic efficacy.
Once in the bloodstream, drugs encounter additional barriers like enzymatic hydrolysis by proteolytic enzymes and plasma protein binding (PPB), which prevent them from penetrating into the tissues. For central nervous system (CNS) active agents, the blood-brain barrier (BBB) poses a significant challenge, limiting the drug's access to the brain. Efflux transporters, particularly P-glycoprotein (PgP), and metabolizing enzymes must also be navigated to reach the target cells effectively.