Final answer:
The process of moving a drug from the distribution site to the bloodstream is primarily passive diffusion, with active transport and endocytosis as additional mechanisms. Oral absorption is influenced by factors like permeability and efflux transporters, and parenteral routes are used when oral absorption is inadequate.
Step-by-step explanation:
The process that brings a drug from the distribution site into the bloodstream is primarily passive diffusion. Drugs are absorbed by passive transfer through the lipid membranes (transcellular absorption) or they can cross between cells through aqueous pores (paracellular absorption). In certain situations, active transport by transporter proteins or endocytosis can play a role. Specifically, about 95% of commercial drugs use passive diffusion, which is a process driven by the concentration gradient without the expenditure of energy. Good permeability across cellular barriers is crucial to maximize the oral absorption of a drug. When oral absorption is inadequate due to efflux transporters like P-glycoprotein (PgP) or metabolism by enzymes, parenteral routes such as intravenous or intramuscular injection are preferred.
In the bloodstream, factors such as plasma protein binding (PPB) and enzymatic hydrolysis affect a drug's ability to penetrate tissues. Only unbound drugs can effectively move into tissues, and drugs with high affinity to plasma proteins may have reduced tissue concentrations and extended half-lives. Drugs that do not enter tissues effectively may be considered for alternative delivery routes or formulation adjustments to improve their bioavailability.